EPA/600/R-97/122

November 1997

Research Plan for

Microbial Pathogens

and 

Disinfection By-Products

in

Drinking Water

U.S.EPA

Office of Research and Development

Office of Water
TABLE OF CONTENTS

Chapter I. Introduction ................................................... 1-1

Purpose ........................................................... 1-1

The Problem ....................................................... 1-1

Regulatory Background .............................................. 1-3

Drinking Water Treatment - Brief Overview ............................. 1-8

Policy Questions and Research Goals ................................... 1-8

Microbial Pathogens - Research Needs ................................. 1-11

Disinfection By-Products - Research Needs ............................. 1-17

Criteria for Priority -Setting ......................................... 1-23

Contents of the Following Chapters ................................... 1-24

Chapter II. Balancing Microbial and DBP Risks: Integrating Research to Support Rule

Development ............................................................ 2-1

Overview of Approach to Balancing Microbial and DBP Risks .............. 2-1

Integrating Research to Support Rule Development ....................... 2-2

Chapter III. Research for Microbial Pathogens ................................ 3-1

A. Background .................................................... 3-1

B. Health Effects Research ........................................... 3-3

C. Exposure Research .............................................. 3-10

D. Risk Assessment Research ........................................ 3-27

E. Risk Management Research ...................................... 3-32

Chapter IV. Research for Disinfection By-Products ............................. 4-1

A. Background .................................................... 4-1

B. Health Effects Research ........................................... 4-3

C. Exposure Research .............................................. 4-19

D. Risk Assessment Research ........................................ 4-29

E. Risk Management Research ...................................... 4-39
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CHAPTER I. INTRODUCTION

Purpose

This document describes the research needed to support EPA’s development of drinking

water regulations for community systems concerning disinfectants, disinfection by-products

(DBPs) and microbial pathogens. It does not specifically address the needs of non-community

systems; however, much of the information that will be generated by this research will be relevant

to non-community systems as well. While the research needs identified in this plan are extensive,

the plan is intended to focus on the key scientific and technical information needed to develop

sound regulations. EPA is committed to conducting a substantial research program that will

address many of the priority research needs identified in the plan. EPA also hopes to use this plan

as a vehicle for discussion with outside groups, including those who participated in the DBP

regulatory negotiation, to reach agreement on the components of the plan. EPA anticipates that

the plan can then be used to promote coordination and cooperation among the various agencies,

private organizations, and universities that are involved in DBP and microbial research. EPA

envisions continuing the stakeholder meetings to facilitate coordination of research.

The Problem

For nearly 100 years, public water supplies have been treated with a variety of chemicals

targeted at the reduction or elimination of infectious disease risk. But risks remain, as evidenced

by the EPA Science Advisory Board’s 1990 ranking of pollutants in drinking water as one of the

highest health risks meriting EPA’s attention. This ranking was based on the exposure of large

populations to known and unknown contaminants, including lead, DBPs, and disease-causing

microorganisms.

The continued occurrence of waterborne disease outbreaks demonstrates that

contamination of drinking water with pathogenic bacteria, viruses and parasites still poses a

serious health risk when treatment is inadequate or when contamination occurs in the distribution

system. Thirty-four outbreaks of waterborne disease were reported in 1991-1992, and the

causative agent was not identified in most of these outbreaks. A 1993 outbreak of
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Cryptosporidiosis in Milwaukee, which resulted in an estimated 400,000 cases of acute

gastroenteritis, represents the largest documented occurrence of disease associated with

contamination of a treated public water supply in the U.S. In addition to these known outbreaks,

many others undoubtedly occur each year but are either unrecognized or unreported. Cases not

associated with an outbreak (endemic or opportunistic disease) may also be significant, but little is

known about the extent to which this is a problem.

To combat waterborne microbial diseases, public water systems disinfect drinking water

with chlorine or alternative disinfectants, such as ozone, chloramines, or chlorine dioxide. 

However, the use of chlorine or other disinfectants, while reducing microbial risks, creates new

potential risks, because compounds known as disinfection by-products are formed during the

water treatment process. A wide variety of by-products have been identified, a number of which

have been shown to cause cancer and other toxic effects in animals under experimental conditions. 

Additionally, some epidemiology studies have suggested that consumption of chlorinated water

may be associated with elevated rates of cancer and adverse reproductive outcomes. In

reviewing these data, however, most experts agree that the scientific evidence is inconclusive with

regard to the significance of adverse health risks from exposure to disinfected waters. 

The challenge in providing safe drinking water today lies in adequately characterizing the

risks and then reaching an acceptable balance among competing risks. Increased disinfection can

reduce microbial risks, but can increase the potential risk from disinfection by-products. The

optimal balance will adequately control risks from pathogens, simultaneously control DBPs to

acceptable levels, and ensure that costs of water treatment are commensurate with public health

benefits. To enable EPA to develop regulations that will achieve this balance, research is needed

to obtain a better understanding of the potential health risks and human exposures to pathogens

and DBPs. Research is also needed on water treatment processes and other means of reducing

these risks.

Regulatory Background

The Safe Drinking Water Act (SDWA) mandates that EPA identify and regulate drinking

water contaminants which may have any adverse human health effects and which are known or

anticipated to occur in public water systems. The SDWA also requires the use of filtration and/or

disinfection for public water supplies that serve most of the U.S. population. Currently, several
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regulations attempt to control for DBPs and pathogens in public drinking water supplies:

• Interim total trihalomethane (TTHM) standard (promulgated 1979) - This standard is

applicable to all community water systems that disinfect and serve at least 10,000 people. 

Systems must achieve less than 0.10 mg/l of total trihalomethanes as an annual average

based on quarterly measurements in the distribution system.

• Total coliform rule (promulgated 1989) - This standard is applicable to all public water

systems. Systems must demonstrate that the frequency of total coliform presence is below

acceptable limits; sampling frequency is based on population served. Small systems which

collect fewer than 5 samples per month must conduct periodic sanitary surveys. 

• Surface water treatment rule (SWTR) (promulgated 1989) - This standard is applicable

to all public water systems that use surface water or ground water under the direct

influence of surface water. Systems must achieve at least 3 and 4 log removal and/or

inactivation for Giardia and viruses, respectively, and if filtration is not part of the

treatment process, the system must meet specific criteria for avoiding filtration.

A more comprehensive regulatory strategy is needed to address microbial and DBP

contaminants in drinking water. The TTHM standard addresses only one class of by-products. 

While control of TTHM during the treatment process may also control formation of other byproducts, the extent of such a relationship is unknown. Additionally the TTHM standard applies

only to larger systems, so the same protection is not afforded to people served by smaller water

systems. While the Total Coliform Rule and SWTR apply to all system sizes, it is not clear that

achieving these standards will provide adequate protection from protozoa, such as Giardia and

Cryptosporidium, especially when a system uses a poor quality source water.

In 1992, EPA initiated a negotiated rulemaking to evaluate the need for additional controls

for microbial pathogens and disinfection by-products. The negotiators included representatives

from state and local health and regulatory agencies, public water systems, elected officials,

consumer groups, and environmental groups. The major goal of the Negotiating Committee was

to develop an approach that would reduce the level of exposure from disinfectants and DBPs

without undermining the control of microbial pathogens. Early in the regulatory negotiation
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process, participants agreed that large amounts of information necessary to understand how to

optimize the use of disinfectants and concurrently minimize microbial and DBPs’ risk were

unavailable. Because of this lack of data the negotiators agreed that there should be a two-stage

DBP rule and Long Term Enhanced Surface Water Treatment Rule (LTESWTR). The Stage 1

DBP rule would be proposed, promulgated and implemented concurrently with the Interim

Enhanced Surface Water Treatment Rule (IESWTR) in order to ensure that microbial risk was

not increased as the Stage 1 DBP rule is implemented. The Stage 2 DBP rule would follow after

additional information on health risk, occurrence, treatment technologies, and analytical methods

were developed in order to better understand the tradeoffs between microbial pathogens risk and

risks from DBPs. Each rule is described below.

The proposed Stage 1 DBP rule included maximum contaminant levels of 0.08 mg/L for

total trihalomethanes, 0.06 mg/L for five haloacetic acids (HAA5), 0.01 mg/L for bromate, and

1.0 mg/L for chlorite along with the best available technologies to control for these DBPs. The

proposed Stage 1 DBP rule also included lower MCLs for TTHMs (40 ug/L) and HAA5 (30

ug/L) as a “placeholder” to assure participants favoring further DBP controls that other members

would return for Stage 2 DBP negotiations. For the Stage 2 DBP rule, the negotiators agreed

that EPA would collect data on the parameters that influence DBP formation and occurrence of

DBPs in drinking water through the Information Collection Rule (ICR). Based on this

information and new data generated through research, EPA would reevaluate the Stage 2 DBP

"placeholder" provisions and repropose, as appropriate, depending on the criteria agreed on in a

second regulatory negotiation. 

The SDWA was reauthorized in 1996. The 1996 SDWA amendments required EPA to

conduct research in several areas including: research to better understand the mechanisms by

which chemicals cause adverse effects; research on new approaches for studying the adverse

effects of contaminant mixtures in drinking water; studies to identify subpopulations that are at

greater risk than the general public from exposure to contaminants in drinking water; and pilot

waterborne disease occurrence studies in at least five major U.S. communities in collaboration

with CDC. EPA has provided special emphasis in this plan to address these statutory

requirements. The amendments also provided an additional $10 million in 1997 for conducting

health effects research on drinking water contaminants. Of this $10 million, about $9 million has

been targeted toward conducting research for microbial pathogens and DBPs.
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The SDWA amendments also established new deadlines for the M/DBP rules. The final

Stage 1 DBP rule and the IESWTR must be finalized by November 1998, while the Stage 2 DBP

rule must be finalized by May 2002 and the LTESWTR must be finalized by November 2000. 

The deadlines for promulgation of the Groundwater Disinfection Rule are between August 1999

and May 2002. The Information Collection Rule was finalized in May 1996, with monitoring

starting in July 1997 and ending in December 1998. 

Long-term 1 enhanced surface water treatment rule (LT1ESWTR) follows. ( Long-term 2

enhanced surface water treatment rule (LT2ESWTR) (final by 5/2002 - not a statutory deadline) 

will be developed to further improve control for pathogens and will be promulgated in

conjunction with Stage 2 of the D/DBP rule in order to prevent increased risk for systems

complying with the Stage 2 DBP rule.) 

• Information collection rule (ICR) (proposed 2/94; final 5/96) - Large public systems

would be required to collect approximately $130 million of occurrence and treatment

information concerning pathogens and DBPs. Information collected under this rule would

be used with research to support the development of the interim and long-term enhanced

SWTR, and Stage 2 DBP rule. 

• Stage 1 Disinfectant/Disinfection By-Products (D/DBP) rule (proposed 7/94; final

11/98) - This rule would be applicable to all community water systems that disinfect and is

intended to reduce risks from disinfectants and DBPs. Systems would be required to

achieve new limits for TTHMs, the sum concentration for five haloacetic acids, bromate,

chlorite, chlorine, chlorine dioxide, and chloramines. Systems using conventional

treatment (sedimentation and filtration) would also be required to achieve percent 

reductions of DBP precursors (measured as total organic carbon), depending upon source

water quality, prior to disinfection.

• Interim enhanced surface water treatment rule (IESWTR) (proposed 7/94; final 11/98)

- This rule would be applicable to all public water systems using surface water or ground

water under the direct influence of surface water that serve populations of 10,000 or

greater. The purpose of this rule is to enhance protection from pathogens, including

Cryptosporidium, and to prevent increases in microbial risk while large systems comply

with the Stage 1 D/DBP rule. Several regulatory options were proposed, including
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systems being required to achieve a) proportionally higher levels of pathogen removal

depending upon pathogen measurements in the source water, and b) fixed level removal

requirements independent of pathogen measurements in the source water. 

• Long-term enhanced surface water treatment rule (LTESWTR) (final by 11/2000) -

This rule, which could include changes to the IESWTR, would extend applicability to

surface water systems serving less than 10,000 people. The purpose of this rule is to

enhance protection from pathogens, including Cryptosporidium, and to prevent increases

in microbial risk for systems serving less than 10,000 people, while they comply with the

Stage 1 D/DBP rule. 

• Stage 2 DBP rule (proposed in part 7/94 with the Stage 1 D/DBP rule; final by 5/2002) - 

This rule would be applicable to all community water systems that disinfect and is intended

to further reduce the levels of risk achieved under the Stage 1 rule. Only tentative limits

were proposed for TTHMs and the sum concentration for five haloacetic acids. 

• Ground water disinfection rule (GWDR) (final between 8/99 and 5/2002) - This rule

would be applicable to all public water systems using ground waters not under the direct

influence of surface water. This rule would require all vulnerable systems to disinfect. 

This rule is intended to enhance protection from pathogens as well as to prevent increases

in microbial risk while systems comply with the Stage 1 D/DBP rule. 

Figure 1 depicts the schedule of rules being developed and the concurrent ongoing activities of

the ICR and research on microbial pathogens and DBPs.
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 Figure 1. Schedule for Expedited M/DBP Rules, Long Term M/DBP Rules, and GWDR Rules and ICR and Research 
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Drinking Water Treatment - Brief Overview

Figure 2 shows the conventional treatment process for surface water supplies along with

the possible points of disinfection. The disinfectants generally used in the United States include

chlorine, chloramines, ozone, and chlorine dioxide and various combinations. Chlorine is the

most common disinfectant used among water systems. About 80% of large water systems

(serving greater than 10,000 people) use chlorine, while almost 100% of smaller systems use

chlorine. Chloramines are used by about 20% of the larger systems, while chlorine dioxide is used

by about 5% of larger systems, and ozone is used by about 2% of the larger systems (the total

does not add to 100% because some systems use combinations of disinfectants). 

The formation of DBPs depends primarily on where in the treatment process the

disinfectants are added and the source water quality parameters. Generally, the later in the

treatment process the disinfectants are added, the fewer DBPs will be formed, all other factors

being equal. The most important water quality parameters that influence the formation of DBPs

include the nature of the source water, such as the content of precursor materials, water

temperature and pH, and conditions under which the disinfectant is used, such as the

concentration, contact time, point of addition, and residual maintained.

Policy Questions and Research Goals

In making decisions on appropriate regulatory levels for pathogens and DBPs in drinking

water, policy-makers will focus on three major questions:

• What are the health risks caused by exposure to microbial pathogens? 

• What are the health risks caused by exposure to disinfection by-products from different 

 treatment processes?

• How can these risks be simultaneously controlled?
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To provide a specific example, a critical issue will be whether ozonation should be encouraged in

place of chlorination. The U.S. has many years of experience with the use of chlorine for

disinfection, and most of the research on DBPs has focused on chlorination by-products. Other

disinfectants, such as ozone, chloramines, and chlorine dioxide, are less widely used than chlorine

and less research has been conducted on their by-products. Recent research indicates that ozone is

much more effective in inactivating Cryptosporidium than chlorine. This may provide an impetus

for many water utilities to switch to ozone as a disinfectant. However, significant uncertainties

remain in assessing the health risks resulting from chlorination and use of alternative disinfectants. 

Before making any major regulatory decisions, policy makers need to know whether the risks from

use of alternative disinfectants are greater than, less than or equal to those from chlorination, and

whether pathogens can be adequately controlled with improvements to the chlorination process.

To support the policy-making process, the research goals are:

1. To identify the health effects caused by DBPs and microbial pathogens in drinking

water.

2. To determine the population distribution of exposure to DBPs and microbial pathogens

to which people are exposed.

3. To assess the risks caused by DBPs and microbial pathogens in drinking water.

4. To evaluate the effectiveness of options for reducing risks from DBPs and microbial

pathogens.

The first three goals are all part of the risk assessment process -- the research proposed in

this plan is intended to fill data gaps and reduce the major uncertainties in current estimates of risks

from microbial pathogens and DBPs. The fourth goal addresses reducing the risks. Research is

needed to fill major gaps in current knowledge about the effectiveness of treatment processes in

simultaneously controlling pathogens and DBPs. 
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The importance of research to support the decision making process for microbes and DBPs

in drinking water is further highlighted by the strong research provisions of the 1996 SDWA

Amendments. This legislation specifically requires EPA to place a high priority on studies

concerning the health effects of Cryptosporidium and DBPs, as well as on studies of

subpopulations at greater risk of adverse effects from exposure to drinking water contaminants. 

The Agency is required to conduct research to support the ESWTR, D/DBP rule, and the GWDR,

particularly in the areas of cancer and reproductive effects (toxicology and epidemiology studies),

and dose-response studies for waterborne pathogens such as Cryptosporidium and Norwalk virus.

To ensure the credibility and soundness of EPA’s regulatory decision-making, it is

imperative that all research is of high technical quality and follows EPA quality assurance

guidelines. EPA policy requires peer review for all major scientific and technical studies that

support regulatory decisions. EPA expects that all research activities supporting this research plan

will undergo appropriate peer review by independent experts.

The following sections provide an overview of research needs for microbial pathogens and

DBPs, in the areas of health effects, exposure, risk assessment and risk management. Each section

begins with highlights of key scientific issues and then lists research questions and research needs.

Microbial Pathogens - Research Needs

Health Effects Research for Microbial Pathogens

Current knowledge of waterborne pathogens is inadequate for assessing their health risks. 

While the disease symptoms caused by pathogens are generally known, limited information is

available on the doses and conditions that produce effects. For example, EPA has estimated risks

from Cryptosporidium using the assumptions that ingestion of a single organism can cause an

infection and that the probability of infection from one organism can be predicted by extrapolation

from higher dose studies. However, there is considerable uncertainty surrounding these

assumptions. Additionally, there are uncertainties with regard to infectivity in susceptible

subpopulations, the significance of the immune response, and the variation among different strains
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of Cryptosporidium in infectivity and virulence. Research is needed on dose-response

relationships, and to evaluate the validity of predicting risks from dose-response curves. 

The incidence of waterborne disease in the U.S. is highly uncertain. Further research is

needed to determine rates of waterborne illness, and, where elevated rates of illness are identified,

to determine whether illness is caused by inadequately treated water or by water quality that has

deteriorated in the distribution system.

Research Questions: 

C What are the waterborne pathogens of public health concern?

C What is the nature and magnitude of disease associated with exposure to these

water borne agents?

Research Needs:

• Information on the pathobiology of infection and disease for waterborne pathogens,

including data on dose-response relationships for various pathogens and different

organism strains, pathogen- and host-specific factors involved in infection and disease,

and effects on different subpopulations.

• Epidemiology studies to characterize endemic and epidemic illness rates, to assess

magnitude of risk, and to provide data for use in verifying risk models.

Exposure Research for Microbial Pathogens

Little information is available on the levels of pathogens that occur in drinking water. 

Current techniques lack the precision and specificity required to measure low levels of pathogens. 

Even with improved measurement techniques, it is very difficult to detect very low levels of

organisms in tap water. To estimate exposures from tap water, EPA expects to rely on
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measurements of pathogens in source water, combined with estimates of the removal and inactivation of pathogens by different treatment processes. For systems relying on ground 

water, information is needed on the survival and transport of pathogens in the subsurface. 

Currently, each of these estimation steps has significant uncertainties.

Research Questions:

• What methods are needed to adequately measure or estimate occurrence of pathogens in

drinking water?

 

• What are the frequencies of occurrence and densities of pathogens in source water, 

finished water, and distribution systems, and what is the population distribution of

exposures to pathogens?

• What are the factors affecting microbial contamination of ground water?

Research Needs:

• Analytical methods to detect and enumerate protozoa, including methods for protozoa

that indicate whether the organism is viable and/or infectious.

• Analytical methods to detect and enumerate viruses in source and finished waters.

• Occurrence information for pathogens in source water and finished waters.

• Assessment of sources of pathogens and the importance of watershed controls.

• Occurrence information for primary and opportunistic pathogens in distribution systems.

• Determination of survival and transport of pathogens in ground water under different

conditions.
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• Assessment methods for protecting groundwater sources from pathogens, including

methods for determining whether “natural disinfection” is adequate.

Risk Assessment Research for Microbial Pathogens

Assessing the risks of waterborne pathogens depends on adequate effects and exposure

information. As indicated above, EPA is likely to rely on estimates of source water pathogen

occurrence, and removal and inactivation by treatment and transport through the distribution

systems to predict concentrations in tap water. In addition, outbreak data will be assessed to

improve our understanding of real time microbial risks especially as it applies to actual source

water conditions, treatment techniques, distribution system integrity and health impacts. This

information will also be used to improve our comparative risk modeling. These data will be

combined with information on dose-response, including sensitive subpopulations, and water

consumption to predict risks.

A comprehensive risk assessment model is needed for assessing the risks from pathogens in

drinking water. The currently accepted risk assessment models were developed for assessing

chemical risks, and do not fully accommodate issues important to the assessment of pathogenic

risks, such as microbe/host interactions, sensitive subpopulations and consideration of secondary

spread of infection. Dose-response models are needed that can address threshold and nonthreshold assumptions, within a modified risk assessment paradigm for microbes.

Research Question:

C How can the risks posed by pathogens in drinking water be characterized? 

Research Needs:

C Modification of risk assessment paradigm for microbial disease.

C Development and application of dose-response statistical models and other
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methods/tools for assessing microbiological disease.

C Methods to characterize risks from mixtures of pathogens, and mixtures of pathogens

and DBPs.

Risk Management Research for Microbial Pathogens

Improved methods for analyzing and protecting source waters are needed to help assure

that treated water is of acceptable quality. Better data on pathogen removal and inactivation

efficiencies of various treatment processes are needed to provide better estimates of risk and to

select the treatment processes with the most potential for risk reduction. Research efforts that

evaluate treatment effectiveness should simultaneously evaluate control of DBPs (see discussion

below). The greatest need is to address the uncertainties surrounding treatment efficiencies for

pathogens by focusing research on those organisms that are most resistant to treatment. For

example, current data indicate that Cryptosporidium is much more resistant to disinfection than

most other waterborne pathogens. In surface waters, by focusing on treatment processes that are

effective for inactivating Cryptosporidium, it is likely that other waterborne pathogens, including

those that may be more infectious or have more significant health effects, will also be effectively

reduced. However, Cryptosporidium analysis is expensive and difficult. Because of the analytical

difficulties in measuring Cryptosporidium in drinking water, an important need is to identify

surrogate parameters for evaluating treatment effectiveness. Potential surrogates include indicator

organisms and engineering process control parameters such as particle size counting and

disinfection operating conditions. In addition, as the existence and significance of new, potentially

dangerous waterborne pathogens are recognized, there is a need to determine the effectiveness of

various treatment systems to control these new organisms.

In ground waters, where protozoa are not expected to occur, it is important to consider

viruses when defining adequacy of treatment. Therefore, there is a need to develop information on

the effectiveness of alternative treatments for controlling viral contamination in ground water

sources. Currently, EPA uses disinfection data on hepatitis A virus (HAV) for estimating

disinfection conditions necessary to inactivate viruses in general. HAV was selected as the target
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virus because it has been implicated in waterborne disease, it is among the viruses with the most

significant adverse health effects, and it is among those most resistant to disinfection. Norwalk

virus may be more resistant to disinfection than HAV and therefore may be more suitable than

HAV for defining adequacy of disinfection.

While protozoa and viruses might be effectively managed at the treatment plant, bacteria

pose a special problem because of their ability to grow in the water distribution system. A number

of the bacteria species identified in distribution systems are opportunistic pathogens, which can

cause illness in certain population subgroups. Treatment processes at the plant can affect bacterial

growth; for example, use of ozone to more effectively control protozoa and viruses may,

depending on the organic content of the water, increase nutrient levels in the treated water and

thus potentially increase bacterial growth in the distribution system. In addition, there is a need to

understand the causes of microbial intrusion into the distribution system and identify effective

approaches to prevent this from happening.

Research Questions:

• How effective are various treatment processes in removing pathogens? 

• How can the quality of treated water be maintained in distribution systems?

• How can source water be protected to ensure that it is consistent with finished water

quality of acceptable microbial risk after appropriate treatment?

Research Needs:

• Methods to analyze and protect source waters.

• Evaluation of the effectiveness of different treatment processes in controlling pathogens,

with a focus on Cryptosporidium, including analysis of the effects of treatment on the

viability/infectivity of Cryptosporidium oocysts that pass through the treatment plant,

and on surrogate indicators of treatment effectiveness. Technologies to evaluate include
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optimization of conventional treatment, filtration, use of sequential disinfectants, and

biological treatment.

C Evaluating the effectiveness of various treatment technologies to control new, potentially

waterborne pathogens as their existence and significance is recognized.

C Development and evaluation of technologies appropriate for small systems, which face

constraints on cost and operational complexity.

C Evaluating the effectiveness of treatment alternatives to control viral contamination in

ground water sources.

• Identification and characterization of factors which influence microbial growth in

distribution systems, and development of strategies to control such growth.

C Understanding the causes of microbial intrusion into the distribution system and

developing cost effective approaches for preventing such intrusion.

Disinfection By-Products - Research Needs

Health Effects Research for Disinfection By-Products

In the 20 years since the discovery of chloroform and other trihalomethanes in drinking

water, a major research issue has been the evaluation of the adverse health effects of DBPs. 

However, significant gaps remain in our knowledge of the actual risks to human populations posed

by the use of disinfectants, especially from alternative disinfectants such as ozone and chlorine

dioxide. A number of epidemiological studies have been conducted, but they have generally been

inconclusive. Some studies have shown no association between consumption of chlorinated water

and cancer, while others have suggested weak to moderate association with cancers of the colon,

rectum and bladder. Epidemiological studies of reproductive effects have been similarly
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inconclusive. Toxicological studies using laboratory animals have shown that a number of DBPs

cause cancer, reproductive toxicity and other effects, but at concentrations higher than typically are

found in drinking water.

Health effects research is needed in three areas. Epidemiological research should be

pursued, with a focus on avoiding the inadequacies in previous studies: study design,

characterization of exposure, and ascertainment of health effects. Toxicology studies on individual

DBPs should be conducted to fill key data gaps and to facilitate extrapolation of animal data to

humans. Additionally, toxicology research using complex mixtures of DBPs would be valuable, if

the technical difficulties in conducting such mixtures studies can be overcome. For example,

epidemiological studies on ozonated water will not be able to evaluate cancer endpoints, because

ozone is a recent technology in the U.S. and long-term exposures have not occurred for large

numbers of people. EPA will have to rely on individual chemical toxicological studies and

mixtures studies to evaluate long-term health effects of ozonation by-products.

Research Questions:

• What are the health effects associated with exposure to DBPs?

– What are the health effects in communities served by disinfected drinking water?

– What is the toxicity of individual chemical contaminants and of mixtures of DBPs?

Research Needs:

• Improved methods for epidemiological research, including better approaches for

assessing exposures and health effects.

• Epidemiology research to provide qualitative and quantitative information on the risks

of cancer, adverse reproductive outcomes, and possibly other health effects that may be

linked to DBP exposures. 

• Toxicology studies on newly-identified or poorly-characterized DBPs to provide basic
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information for traditional hazard identification and dose-response assessment

• Pharmacokinetic and mechanistic data to facilitate the extrapolation of animal data to

humans. 

• Animal studies on well-defined and complex mixtures of DBPs to help bridge the gap

between epidemiology studies and single-chemical toxicity studies. The goal of these

studies would be to assess DBP interactions and to compare the potential toxicity of

drinking water preparations that are closer in composition to "real-world" mixtures.

Exposure Research for Disinfection By-Products

DBPs are formed when disinfectants, for example chlorine or ozone, are added to source

and drinking water to control microbiological organisms. Chlorine, the most widely used and

studied disinfectant, reacts readily with humic substances from decaying animal and vegetable

matter (precursors) as well as organic contaminants, i.e. pesticides, and produces a variety of

chlorinated products. When bromide ion is present, as it is in most source waters to a greater or

lesser degree, brominated and mixed chlorobromo DBPs are also produced. Ozone adds

oxygenated species as does chlorine dioxide. Another disinfectant, chloramine, introduces the

possibility of nitrogen containing byproducts such as cyanogen chloride.

Over 100 different compounds have been detected in drinking water, most of these

resulting from the use of chlorine. Less is known about by-products from ozone and chlorine

dioxide. For example, it was only recently recognized that ozone disinfection can produce

bromate, an ion which may pose significant health risks. The characteristics of the source water,

the type of disinfectant used, and how the disinfectant is used are all factors which influence the

types and quantities of by-products formed. 

Current exposure information is inadequate for conducting a quantitative exposure

assessment for the majority of DBPs. Research is needed to better characterize the by-products
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formed from different treatment processes, especially from alternative disinfectants. Better

analytical methods are needed to assess the frequency and magnitude of occurrence of DBPs,

particularly for polar, water soluble and non-volatile DBPs. Because of limited methods, there is a

paucity of exposure data. We do know, however, that the wide range of disinfection methods and

background constituents in water supplies will result in a wide range of exposure differences.

Research Questions

• What methods are needed to adequately measure occurrence of DBPs in drinking

water?

 • What levels of DBPs are people exposed to via their drinking water supplies, and what

is the population distribution of exposures?

Research Needs:

• Improved methods of analysis for DBPs of concern, including practical methods for

chemicals likely to be regulated in the near future, and research methods to aid in the

discovery and characterization of DBPs

• Identification of new DBPs, particularly from alternate disinfectants

• Data on exposures to DBPs to develop, improve, and validate exposure models

Risk Assessment Research for Disinfection By-Products

Determining the health risks caused by DBPs is a critical part of the DBP research program

-- current evidence is inconclusive, and the implications for water treatment expenditures are

significant if lower levels of DBPs are required. As indicated above, some epidemiological studies

have suggested that elevated rates of cancer may be linked to consumption of chlorinated water. 

Estimates of excess cancer risk vary from 0 to 10,000 or more cancer cases per year when

extrapolated to the U.S. population as a whole. This wide variation in risk estimates results from
1-21

the application of different methods for estimating risks and different exposure assumptions. 

Narrowing the broad range in cancer estimates will depend on health effects and exposure

research, and on advances in risk assessment methodology. In addition to the uncertainties

surrounding cancer risk estimates associated with these chlorinated water studies, uncertainties

exist for other risks such as reproductive and developmental effects.

The traditional risk assessment process has been focused on the evaluation of risks from

exposure to an individual chemical or members of a specific class of chemicals. But exposure to

DBPs in drinking water, as is true for many other environmental exposures, is really exposure to a

complex mixture of chemicals. Assessment of these compounds or classes of compounds as

components of their source water could have a meaningful impact on the understanding of the

actual risks resulting from exposures to these various mixtures. The risk assessment should

therefore take into account possible interactions between chemicals and evaluate the impact on

health risks.

Research Questions

 • How can we better characterize the risk posed by exposure to specific DBPs in drinking

water?

 • How can we characterize the risk posed by exposure to multiple or complex mixtures of

DBPs?

 • How can the risks from chemicals and microbes be compared?

Research Needs

• For individual chemicals, refinement and application of new models for estimating

cancer and noncancer risks, in particular risks associated at exposures typically found in

drinking water.

• Improved estimates of risk using epidemiologic data from previous and ongoing studies,

incorporating improved estimates of exposure where possible.
1-22

• For mixtures of chemicals, application of new methods for assessing risks that include

characterization of chemical interactions.

C Assessment of the comparative toxicity of DBPs within classes or families of

compounds and also between families.

• For chemicals and microbes, a framework for assessing and comparing risks from

different treatment options.

C Better methods for screening and prioritizing potential risks.

Risk Management Research for Disinfection By-Products

Better data are needed on how to control DBPs formed by different treatment processes. 

Simultaneously, candidate treatment processes must be evaluated for control of microbial

pathogens. Treatment options include: optimizing conventional treatment; switching to alternate

disinfectants, such as ozone; use of granular activated carbon (GAC); or use of membrane

technology. The range in treatment costs for the different options is tremendous. EPA has

estimated that the increased household costs for systems serving 250,000 people and using

conventional treatment would be $5/year (optimized treatment), $10/year (ozone/ chloramination),

$60/year (GAC), or $120/year (membrane technology) depending upon which technology might be

needed to comply with new DBP standards. For a typical system serving 2,500 people and using

conventional treatment the household costs could increase by $10/year (optimized treatment),

$60/year (ozone/chloramination), $270/year (GAC or membrane technology) depending upon

which technology might be needed. Clearly, research that could lead to improvements in

conventional treatment and could demonstrate that acceptable levels of pathogens and DBPs can

be achieved will be highly cost-effective.

Current regulations only set a limit for total trihalomethanes, relying on the assumption that

practices that control formation of these chemicals will also control other by-products. Research is

needed to determine whether this assumption is valid, or whether other surrogate parameters can

act as good indicators of DBP control. Depending on the outcome of the health research, other

DBPs may become of greater concern.
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Research Question

 • How effective are various treatment processes in minimizing the formation of DBPs?

Research Needs

• Evaluate processes that prevent DBP formation by reducing precursor compounds in

source water.

• Evaluate use of different disinfectants in limiting DBP formation.

• Evaluate promising innovative technologies for small systems to control precursors and

DBP formation.

Criteria For Priority Setting

Chapters III and IV of this plan identify research projects intended to meet the research

needs described above. The following criteria were used to select the research projects that are

included in this plan. All projects included in the plan are generally considered as high priorities

for research. However, to provide a sense of relative priority for the projects identified here,

priority rankings of High, Medium or Low were developed. The criteria used for ranking are listed

in descending order of importance:

• High risk - The research is likely to elucidate the concentrations, occurrence, or

toxicity/pathogenicity of a contaminant, where preliminary information suggests that it

may have a significant impact on public health.

• High uncertainty - The research is likely to reduce significant uncertainties associated with

current assessments or risk reduction technologies.

• Regulatory relevance -The likelihood is high that research will lead to regulatory criteria

that reduce the risk to public health in a cost-effective manner.

Additional considerations which were relevant in setting priorities for some projects:
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• Short-term and long-term research needs - An appropriate balance is achieved between 

research that addresses specific short-term needs (many objectives must be fulfilled with a

3-5 year time frame to support regulation development) and research that addresses more

strategic, long-term needs (e.g., developing new methodologies for more comprehensive

assessments of exposure to drinking water contaminants).

• Linkage to other efforts - The research is complementary to related research efforts in

EPA (e.g., risk assessment methods research), other federal and state agencies, and the

private sector.

• Anticipatory research - The results of the research will help anticipate future drinking

water problems.

• Wider applicability - The results of the research may be extended to other drinking water

or environmental issues. 

Contents of the Following Chapters

Chapter II describes how the proposed research projects presented in Chapters III and IV

will be used to support the various drinking water regulations described above. Chapter II briefly

describes how the research will assist in estimating national/local costs and benefits of the

regulations and how this information can be used by decision makers to balance the risks from

microbial pathogens and DBPs.

 Chapter III and Chapter IV describe research needed for microbial pathogens and DBPs,

respectively. Within Chapters III and IV, specific research projects have been organized into the

following categories: Health Effects, Exposure, Risk Assessment, and Risk Management. In some

cases, the proposed projects cut across these categories and a coordinated, interdisciplinary

approach is required. An example is project HE.M.7, Characterization of Endemic Disease: Health

Effects Associated with Differences in Source Water Quality and Treatment Process, which would

include health effects, exposure and risk management research. 

The “State of the Science” sections for each major research question describe past and

current research efforts by EPA and others. In the “Research Topics and Priorities” section,

projects that are listed are primarily research which is needed but not yet underway. EPA expects
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to be able to fund a significant portion, but not all, of these projects. EPA’s ongoing and

completed research has been included in the project listings, as this research should be considered

in the debate about relative priorities.

The intent of this research plan is to propose research that will answer the research

questions presented generally in Chapter I and more specifically in Chapters III and IV. However,

the extent to which some of these questions can be answered may significantly depend on upon the

results of the research. The plan attempts to indicate, in general terms, how research directions

and priorities may change depending on outcomes of research.
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Chapter II. Balancing Microbial and DBP Risks: 

Integrating Research to Support Rule Development

Chapters III and IV will discuss research needs and projects to address those needs for

each of four research topic areas (health effects, exposure, risk assessment, and risk management)

as they relate to achieving a better understanding of risks and control of those risks posed by

pathogens and DBPs. The purpose of Chapter II is to indicate how research will be used to

support the development of the DBP Stage 1 rule, DBP Stage 2 rule, IESWTR, LT1ESWTR,

LT2ESWTR, and GWDR.

Overview of Approach to Balancing Microbial and DBP Risks

EPA is attempting to develop regulations that will result in the proper balance between

controlling risks from pathogens and DBPs. Figure II.1a shows that in general as the level of

disinfection applied to drinking water increases, the risk from exposure to pathogens decreases

while the risk from DBPs increases. Clearly, the type of source water treated, technology applied,

microorganism removed and disinfectant used, will influence the slope of the risk function. Figure

II.1b shows how cost/benefit analysis ideally might be used to minimize social costs associated

with the application of technology to minimize exposure to pathogens and DBPs simultaneously. 

As the level of treatment to lower exposure from both DBPs and pathogens increases, the cost of

treatment increases while the potential cost of health damages decreases. 

The ability to determine the proper balance between controlling risks from pathogens and

DBPs requires enormous amounts of data, some of which will be developed as part of the

research described in this document. Since the occurrence of pathogens and DBPs in drinking

waters vary greatly, it is very difficult to estimate total national risks or total national risk

reductions that might result from different regulatory options. Also, regulatory decisions which

lead to minimum social costs at the national level may not be justified if they lead to large adverse

changes in social costs at the local level. Recognizing these problems, EPA is developing an

approach for estimating national and local costs and benefits (regulatory impact analysis -RIA)

that should support meaningful regulatory decisions. The results from the research described in

this plan, the ICR, and supplemental surveys will provide answers to many of the research

2-2

questions posed in Chapter I and will provide input for estimating the costs and benefits of the

various rules and in balancing the risks from pathogens and DBPs.

Integrating Research to Support Rule Development

Following is a discussion, by rule, of key regulatory issues and how the research plan

would be used to help resolve these issues. Research projects are listed that are either completed,

currently ongoing by EPA, or planned according to the rule they would most significantly

support. A key question in the development of the drinking water regulations is whether the

research will be completed in time to support the development of the various M/DBP rules. 

Tables 2-1, 2-2, and 2-3 provide the dates by which the research will be completed and the text

under each rule provides a discussion on when the research is needed. Before discussing the

research projects it is important to first understand how the research will be used in developing

regulations.

The overall goal of the SDWA is the establishment of drinking water standards that will

protect public health. The SDWA specifies that EPA establish Maximum Contaminant Level

Goals (MCLGs) for contaminants at which no known or anticipated adverse effects on the health

of persons occur and which allow an adequate margin of safety. MCLGs are nonenforceable

health goals based predominately on health effects data and estimates of occurrence/exposure for

the contaminant. Establishing MCLGs for a DBP is the first step in deciding that the contaminant

poses a human health risk that requires some control. When setting MCLGs for contaminants in

drinking water, EPA must also establish a Maximum Contaminant Level (MCL) that is as close

to the MCLG as feasible. The SDWA defines feasible as “the use of best available technology,

treatment techniques and other means which the Administrator finds, after examination for

efficacy under field conditions and not solely under laboratory conditions, are available (taking

cost into consideration)”. To set an MCL, it has to be both technologically and economically

feasible to monitor the contaminant in the drinking water. In cases where monitoring is not

feasible, EPA is authorized to develop a treatment technique requirement instead of an MCL. 

The treatment technique requirement must prevent known or anticipated adverse effects on the

health of persons to the extent feasible. Because of the difficulties in monitoring for Giardia,
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viruses or Cryptosporidium, both the 1989 SWTR and the 1994 proposed IESWTR are treatment

technique rules. Each rule must also establish compliance monitoring requirements to ensure the

contaminant is being accurately characterized.

Under the 1996 amendments to the SDWA, EPA may set an MCL at a level other than the

feasible level (as defined in the statute) if the technology or treatment technique would result in an

increase in the health risk from other drinking water contaminants. In cases where a treatment

technique requirement is set at a level other than the “feasible level”, EPA is required to minimize

the overall health effects. This provision is relevant to the LT2ESWTR and Stage 2 D/DBP rule,

because the control of microbial pathogens may increase the risk to DBPs and the control of

DBPs may increase the risk from microbial pathogens. It is therefore important that EPA have

adequate knowledge of the extent to which, under given conditions, reduction of one

contaminant results in an increase in another. In the case of the LT2ESWTR, this means

understanding under what conditions and the extent to which changes in relevant DBPs result

from different microbial treatment technique requirements, such as the inactivation of

Cryptosporidium. Other contaminants or parameters whose levels could be increased by high

disinfectant doses under certain conditions include arsenic, lead, and assimilable organic carbon

(AOC). AOC provides the nutrients which promote microbial growth in the distribution system,

possibly resulting in a series of problems that are not well understood (e.g., growth of

opportunistic pathogens and coliform bacteria, rapid disinfection residual decay, and corrosion).

As discussed above, the two primary inputs into the MCLG are health effects data and

occurrence/exposure data. Although some data currently exist on the occurrence levels of DBPs

and pathogens, the majority of new occurrence data for DBPs will come from the ICR and the

majority of new occurrence data for pathogens will come from the ICR, "mini-ICR" and

supplemental surveys. When developing MCLs and/or treatment techniques the main inputs

include: the availability of analytical methods; effectiveness of treatment technologies to control

the contaminants; and the cost of these technologies. When designing compliance monitoring

strategies the main inputs include the costs of monitoring and the ability of monitoring to

accurately characterize the levels of the DBPs at consumers taps.
2-4

Surface Water Treatment Rules

The IESWTR was proposed in July 1994. The final IESTWR is required by November

1998. The purpose of the IESWTR is to prevent increases in microbial risk and to enhance

control for Cryptosporidium while systems serving 10,000 or more people comply with the Stage

1 D/DBP rule. The IESWTR applies to surface water systems serving at least 10,000 people. 

The Long-Term 1 ESWTR (LT1ESTWR) will apply to surface water systems serving less than

10,000 people and is scheduled to be proposed in September 1999 and promulgated in November

2000. This rule is intended to improve physical removal of Cryptosporidium and prevent

significant increases in microbial risk for smaller systems while they also comply with the Stage 1

D/DBP rule. The LT2ESWTR will be developed to further improve control for pathogens and

will be promulgated in conjunction with the Stage 2 D/DBP rule in order to prevent increased risk

for systems complying with the Stage 2 rule. 

Participants in the DBP regulatory negotiations were concerned about the extent to which

microbial risk might increase if systems were to comply with new DBP standards. RIA modeling

analysis indicated that more than one percent of the population in some systems could become

infected with Giardia if systems were required to meet more stringent DBP standards and comply

with the existing SWTR (i.e., providing 3 logs removal whereas 5 logs might be appropriate).

While this analysis had significant uncertainties concerning national cyst occurrence and

assumptions needed in the risk assessment, the potential increased microbial risks that could result

from DBP regulation were significant. 

In another RIA analysis, potential impacts for different Stage 1 DBP rule options were

evaluated assuming that systems would simultaneously have to provide higher levels of treatment

for Giardia (versus the minimum of 3 logs required for all systems under the SWTR) as a function

of higher Giardia concentrations in the source water. The goal of such a theoretical Giardia based

rule, one of the options proposed in the IESWTR, was for systems to provide adequate treatment

to achieve a risk level of less than one infection of Giardia per 10,000 people per year. It was

assumed that if systems were required to meet such a risk level, they would not incur significant

increases in microbial risk while making treatment changes to comply with the Stage 1 DBP rule. 

The RIA for this Giardia based rule estimated that 400,000 to 500,000 infections of Giardia could
2-5

be avoided per year at a cost of about $400 million per year. 

A major shortcoming with the above estimates, in addition to the uncertainties in the

assumptions needed for the analysis, was the inability to include impacts for regulating

Cryptosporidium since occurrence, treatment effectiveness data, and dose response information

was missing. Cryptosporidium may be the preferred target organism for defining minimum levels

of treatment because it is substantially more resistant to disinfection than Giardia. A

Cryptosporidium based rule similar to that described for Giardia would probably be significantly

more costly. Also, such a rule could trigger significant shifts by the industry to greater use of

alternative disinfectants such as ozone (since they appear more effective than chlorine for

inactivating Cryptosporidium), decreasing byproducts from chlorine but increasing other

byproducts. 

LT2ESTWR

The majority of the research described in this research plan will be used when designing

the LT2ESTWR. The regulatory needs for the LT2ESTWR include: 1) a better understanding of

the magnitude of the risk from Cryptosporidium and other pathogens; 2) a more accurate

characterization of the occurrence of Cryptosporidium; 3) an evaluation of the potential for using

indicators to determine pathogen occurrence; and 4) the removal and inactivation efficiencies of

different treatments and the effects on the distribution system.

EPA is considering at least three different approaches (and combinations of these

approaches) to further regulating Giardia, Cryptosporidium, and viruses (and indirectly regulating

other pathogens) in the LT2ESWTR: fixed treatment approach; proportional treatment approach;

and watershed-based approach. Each of these approaches has different, but also similar,

information requirements. The fixed treatment approach would require all systems to provide at

least the same minimum level of treatment (same log reduction of pathogens); the proportional

treatment approach would require systems to provide a minimum level of treatment at all times

based on pathogen levels in the source water; and the watershed-based approach would require

systems to provide a minimum level of treatment at all times based on a combination of factors

that indicate the level of the source water’s vulnerability to pathogen contamination. Hybrids of
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these regulatory approaches are also under consideration, e.g., a fixed treatment approach for one

pathogen and a proportional level of treatment for another pathogen. Similarly, different

regulatory approaches might be considered for different water body types (e.g., one type of

requirement might be appropriate for quiescent waters while another type might be appropriate

for running waters).

The advantage of the proportional and the watershed-based treatment requirements is that

the drinking water treatment required is based on the individual system’s source water quality. 

The treatment would prevent exposure to unacceptable microbial risk and would avoid

unnecessary disinfection and associated DBPs. By contrast, the fixed treatment requirement - the

one size fits all - could require some systems with high quality source water to provide

unnecessary treatment at a high cost to the consumers, while others with highly contaminated

source waters might provide inadequate treatment. 

In its evaluation of a regulatory option under either of these three structural approaches,

EPA plans to use nationwide system-specific data on source water quality and water treatment, as

well as research results, to estimate the changes in treatment that would be necessary to meet

target microbial risk levels, or conversely to estimate the risks associated with given treatment

requirements. In simple terms, the process of relating treatment to microbial risk can be divided

into three steps: step 1) establishing the level of contamination in the source water (the

occurrence of the pathogen), either using information on pathogen concentrations or based on

pathogen “indicators”; step 2) estimating the reduction in pathogen occurrence due to treatment

of known efficacy; and step 3) applying an exposure and dose response model to the resulting 

pathogen occurrence to estimate the risk of infection. An additional step in this regulatory process

will be to determine the level of DBPs associated with the different treatment requirements. 

While all of these steps will involve differing degrees of uncertainties, this analytical approach

should provide a characterization of relative levels of exposure to microbes (and DBPs) based on

source water quality and treatment provided. EPA believes that results of ongoing research

studies will contribute to reducing some of the uncertainties in classifying source water pathogen

risk, quantifying treatment effectiveness, and measuring health effects due to pathogen exposure.

Table 2.1 summarizes research projects completed, ongoing by EPA or not yet funded that
2-7

would support the development of the LT2ESWTR. These projects are described more fully in

Chapters III and IV. The development of cost/benefits as part of the RIA requires information on

the risk estimates of predicted pathogen levels in treated waters, occurrence of pathogens in

source waters, and removal and inactivation efficiencies for different technologies. 

To develop a better understanding of the magnitude of the risk from Cryptosporidium and

other pathogens, it will be necessary to develop a better understanding of the dose response to

Cryptosporidium and different pathogens, and how the risk varies according to strain and immune

system response. There are several studies which are evaluating the dose-response to

Cryptosporidium (HE.M.1-4 and by AWWARF and CDC). These studies should provide a good

understanding of the range of responses to Cryptosporidium although the probability of being

exposed to one strain versus another is likely to remain uncertain. Several projects are examining

the high and low dose-response, immune system effects and clinical symptoms associated with

exposure to the caliciviruses, Norwalk virus and Snow Mountain Agent (HE.M.5). In addition to

dose-response studies, epidemiology studies may be useful for verifying whether the risk estimates

using traditional risk models are accurate and can provide information to help evaluate

appropriate levels of protection (HE.M 7-10). They may also identify the factors relevant to

reducing the disease burden from drinking water. AWWARF and CDC are also sponsoring

research in these areas. The research described above should be completed in time for the

LT2ESTWR.

In order to more accurately characterize the occurrence of Cryptosporidium and Giardia in

raw and finished water, a more precise, accurate, facile and low cost method is needed for the

LT2ESTWR. EPA is conducting a large amount of research to develop a better method for

protozoa (EX.M.1-6). AWWARF and CDC are also conducting substantial research to develop a

better method for detecting protozoa. EPA believes the prospects are good for a method to be

available in time for the proposed LT2ESWTR, that can adequately limit misclassification rates of

source water Cryptosporidium concentration. There is also research into developing better

methods for caliciviruses such as Norwalk (EX.M.8-9) and studies to improve methods are

planned for adenoviruses, coxsackiviruses, and hepatitis A (EX.M.8).
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The ICR will provide 18 months of data on the occurrence of Giardia, Cryptosporidium,

and viruses from close to 350 different water treatment plants. Other data to be collected include

data on turbidity, coliforms, water resource type (river, reservoir/lake) and whether watershed

control is practiced. EPA will also conduct supplemental surveys which will complement the ICR

data to provide source water microbial occurrence data necessary to support the regulatory

impact analysis for different LT2ESWTR options. The “mini-ICR” will also collect pathogen

occurrence data (EX.D.11) and will provide a range of data to assess pathogen occurrence

variability and develop a better understanding of differences between worst case pathogen levels

and other statistical endpoints (e.g., 90th percentile, median). AWWARF and the USDA are

conducting several studies on the survival of Cryptosporidium in the environment.

Another important aspect of estimating Cryptosporidium occurrence in source water is its

variability and the co-occurrence of Cryptosporidium with other microorganisms that could

possibly serve as indicators. Indicators could be especially important for smaller systems where

an approach based on indicators of pathogen occurrence would be ideal because of the cost and

the complications associated with pathogen monitoring. To determine which indicators, or

combination of indicators, correlate best with pathogen occurrence, EPA will analyze the results

of the 18 monthly source water samples collected by systems under the ICR and the results of the

related supplemental surveys. In addition, the “mini-ICR” will examine the use of indicators

(EX.D.11). The information from the “mini-ICR” should facilitate development of source water

pathogen categories based on indicators and watershed characteristics (e.g., the range of pathogen

contamination associated with certain fecal coliform distributions in the raw water of a system

served by a river source).

From a regulatory standpoint it is important to be able to determine the level of treatment

that is achieved by a particular treatment process under different water quality and operating

conditions (i.e., performance indicators are needed to establish pathogen removal and

inactivation). Typically, performance indicators used in the context of microbial treatment

technique requirements are filter effluent turbidity for physical removal and CT values

(concentration of disinfectant in mg/L multiplied by the contact time in minutes) for pathogen

inactivation. These and other indicators (and combinations thereof) need to be evaluated to
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determine how they can be used to demonstrate that the required level of treatment is being

achieved. EPA expects that ongoing research on treatment optimization to remove pathogens and

on indicators of treatment effectiveness will contribute information to establish the level of

physical pathogen removal and to develop regulatory performance criteria and associated

monitoring requirements (RM.M.1-7). Regarding regulatory inactivation requirements of

pathogens, research on the disinfection of Cryptosporidium is a high priority for LT2ESWTR

(RM.M 8-10). ICR data may also be used to validate gross assumptions on treatment

effectiveness if it is determined that this is possible once the ICR data is received and reviewed. 

In addition to EPA’s research, AWWARF is conducting a considerable amount of research in

this area (see related projects). As better design and operating parameters become available, they

will be used in an existing water cost model to estimate costs for systems to achieve the

removal/inactivation requirements for different regulatory options. Data from these projects

would also be used for developing guidelines by which utilities could estimate

removal/inactivation efficiencies. The major work in this area should be completed in time for the

LT2ESTWR.

There are several projects that will be completed in time for the LT2ESTWR that would

help determine the health risk significance from bacterial growth in the distribution system and

remedial treatment or operational strategies (EX.M.14-22 and RM.M.14-27). Results from these

efforts would determine what amendments to the SWTR and IESWTR or changes to related

guidance might be needed to reduce risks from contamination from the distribution system. 
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TABLE 2.1: RESEARCH TO SUPPORT THE LT2ESWTR

Expected Priority

Completion

Date

A.. HEALTH EFFECTS RESEARCH

1. Pathobiology of Infection and Disease for Most Important Waterborne Pathogens

 HE.M.1 - Infectious dose of Cryptosporidium 1997 H

 HE.M.2 - Validity of dose-response model for Crypto in animals Proposed H

 HEM..3 - Cryptosporidium virulence study using different strains 1998 H

 HE.M.4 - Cryptosporidium infectious dose in normal/immuno-compromised 1999 H

animals

 HE.M.5 - Infectious dose of Norwalk virus 2000 H

 HE.M.6 - Infectious dose of other priority pathogens Proposed M

AWWARF Related Projects

177 - Association between Cryptosporidium in finished water & 1997

Cryptosporidiosis in population

 354 - Cryptosporidium parvum: Surrogate human pathogenicity animal model 1999

using swine

2. Characterization of Epidemic and Endemic Waterborne Disease

 HE.M.7 - Characterization of endemic disease (with AWWARF) 2000 H

 HE.M.8 - Immunological assay for assessing exposure in epi studies (with 1998 H

AWWARF)

 HE.M.9 Investigations of waterborne disease outbreaks Ongoing H

 HE.M.10 - Surveillance tool for waterborne disease outbreaks Completed H

AWWARF Related Projects

168 - Prospective Epi study of waterborne microbial disease (with EPA) 97

268 - Fingerprinting techniques for opportunistic pathogens & illness 98

B. EXPOSURE RESEARCH

1a. Microbial Methods - Protozoa

 EX.M.1 - Immunological techniques for protozoa 1999 H

 EX.M.2 - Gene probes for detection of viable Cryptosporidium oocysts 1998 H

 EX.M.3 - Cultural method for Crypto. in environmental samples Completed H

 EX.M.4 - PCR methods for Giardia and Cryptosporidium (CRADA) 1997 M

 EX.M.5 - Protozoa methodology protocol development workshop Completed H
Expected Priority

Completion

Date

2-11

 EX.M.6 - Comparison of methods for Giardia/Cryptosporidium in water 2000 H

 EX.M.7 - New protozoa agents 1998 H

AWWARF related projects

160 - Vital stain for Giardia and Cryptosporidium Completed

162 - UV-VIS spectroscopy for rapid on-line detection of protozoa 1998

253 - Viability method for Giardia and Cryptosporidium 1998

259 - Improve the IFA method for Giardia and Cryptosporidium 1998

283 - Detection of Giardia & Cryptosporidium by flow cytometry Completed

351 - Cryptosporidium parvum viability assay 1998

358 - Cryptosporidium and Giardia antibody protocol 1998

364 - New approaches for isolation of Cryptosporidium and Giardia 1998

366 - Assessment of molecular epidemiology of waterborne Crypto. with respect 1998

to origin

395 - Compare study of methods for assessing viability/infectivity of Crypto. in 1999

U.S./U.K.

1b. Microbial Methods - Viruses 

 EX.M.8 -Application of PCR technologies and gene probes 1999 M

 EX.M.9 - Norwalk virus 2000 H

 EX.M.10 - Methods for emerging viruses Proposed H

AWWARF projects

292 - Rapid PCR-based monitoring of entero viruses 1998

345 - Detection and occurrence of caliciviruses in drinking water 1999

612 - Analysis of viruses by gene probe Completed

726 - Viral and microbial methods for groundwater 1997

2a. Microbial Exposure - Pathogen Occurrence

 EX.M.11 - Intensive eval. of micro. constituents/treatability in surface source 2000 H

waters (mini-ICR with Research Council)

 EX.M.12 - Identification of viruses resistant to disinfection Proposed M

2b. Microbial Exposure - Watershed Control

 EX.M.13 - Distinguish animal versus human sources 1998 M

AWWARF related projects

251 - Evaluating of sources of pathogens and NOM in watersheds 1998
Expected Priority

Completion

Date

2-12

2c. Microbial Exposure - Opportunistic Pathogens in Distribution System

 EX.M.14 - Occurrence of Mycobacterium 1998 H

 EX.M.15 - Occurrence of heterotrophic bacteria with virulence characteristic 2001 H

 EX.M.16 - PCR method for Legionella 1998 L

 EX.M.17 - Pathogenicity of heterotrophic bacteria in drinking water. 1998 H

 EX.M.18 - Occurrence of opportunistic pathogens in biofilms Proposed M

 EX.M.19 - Opportunistic pathogens assoc. with (POU)/ (POE) filter effluents Proposed M

 EX.M. 20 - Potential pathogenicity of heterotrophic bacteria eluted from Proposed H

point-of -use GAC filters

 EX.M.21- Occurrence of newly emerging pathogens 2000 H

 EX.M.22 - Exposure as a function of population distribution 1999 H

C. RISK ASSESSMENT RESEARCH

1. Risks from pathogens

 RA.M.1 - Dev. comprehensive microbio risk assess paradigm for water 2000 H

 RA.M.2 - Evaluation/Application of various dose-response models 1998 H

 RA.M.3 - Evaluation and application of methods to assess risk associated with 2000 M

exposures to multiple pathogens, routes, and durations

AWWARF Related Projects

801 - Microbial risk assessment for drinking water Completed

D. RISK MANAGEMENT RESEARCH

1a. Pathogen Removal - Optimization of Conventional Treatments

 RM.M.1 - Filtration studies for controlling pathogens 1999 H

 RM.M.2 - Filtration removal of protozoa and indicators 1998 H

 RM.M.3 - Optimize conventional treatment for removal of oocysts 1999 H

 RM.M.4 - Filtration damage viability studies 1999 H

 RM.M.5 - Evaluate disinfection and optimization in full-scale 1 plants 1997 H

 RM.M.28 - Evaluation of the effectiveness of conventional treatment Proposed M

processes on removing and inactivating emerging pathogens

AWWARF Related Projects

155 - Enhanced/optimized coagulation for removal of microbial contaminants 1997
Expected Priority

Completion

Date

2-13

352 - Treatment options for giardia/crypto./ and other contaminants in recycled 1998

backwash water

363 - Application of pathogen surrogates measures to improve plant performance 1998

608 - Lime softening processes for Giardia and viruses Completed

636 - Evaluation of roughing filter design variables Completed

703 - Optimization of filtration for cyst removal Completed

834 - Balancing multiple water quality objectives 1997

1b. Pathogen Removal - Effectiveness of Different Filtration Processes

 RM.M.6 - Biological treatment for control of oocysts 2000 H

 RM.M.7 - Filtration techniques other than conventional treatment 2000 M

 RM.M. 29 - Evaluate filtration processes to remove emerging pathogens Proposed M

AWWARF Related Projects

181 - Biological particle surrogates for filtration performance eval. 1997

Particle Counting as Indicator of Treatment Efficacy

266 - Quantitative particle count method development: standardization, sample 1998

stability

291 - Particle Image Velocimetry 1998

423 - Joint project on treatment process selection: particle removal optimization Completed

835 - Practical guide to on-line particle counting Completed

908 - National assess. of particle removal by filtration Completed

Membrane Technology for pathogen removal

264 - Integrated multi-objective membrane systems microbes/DBP precursors 1999

817 - Membrane filtration techniques for microbe removal Completed

Microbial effects of biological Filtration

263 - Colonization of biologically active filter media with pathogens 98

917 - Microbial effects of biological filtration (Don Reasoner on PAC) Completed

1c. Pathogen Removal - Effectiveness of Disinfection for Inactivating Pathogens

 RM.M.8 - Control of Norwalk virus by chlorine and ozone Proposed H

 RM.M 9 - UV disinfection efficiencies for Norwalk Virus Proposed H

 RM.M.10 - Inactivation of Giardia & Crypto by sequential disinfectants 1999 H

 RM.M.31 - Evaluate disinfection processes to inactivate emerging pathogens Proposed M

AWWARF Related Projects

Disinfection
Expected Priority

Completion

Date

2-14

262 - Booster disinfection for pathogen and DBP control 1998

525 - Demo scale eval. of PEROXONE evaluation for disinfection, DBPs 1997

702 - Devt. and validation of rational design methods of disinfection Completed

Disinfection of Protozoan Cysts - Inactivation Studies

151- Cyst and oocyst survival in watersheds and factors affecting inactivation 1997

273 - Synergistic effects of multiple disinfectants (Gene Rice on PAC) 1998

282 - Innovative electrotechnologies for Crypto inactivation 1998

375 - Utility Giardia and Crypto inactivation study - Southern Nevada Water 1998

Authority

731 - Ozone disinfection of Giardia and Crypto Completed

906 - Effect of various disinfection methods on inactivation of Crypto Completed

Disinfection Evaluation and Design

630 - Full scale ozone contactor evaluation Completed

632 - Modeling dissolved ozone in contactors Completed

1d. Pathogen Removal - Small Systems Technologies

 RM.M.11 - Cryptosporidium removal using bag filters 1998 H

 RM.M.12 - Cost effectiveness of prefiltration for ultrafiltration unit 1999 H

 RM.M.13 - Development/test innovative technologies for small systems 1999 H

2a. Distribution Systems - Indicators for Control of Pathogens in Biofilms and Pipe Sediments

 RM.M.14 - Bacteria interference w/detection of coliforms and E. coli Proposed M

AWWARF Related Research

429 - Male-specific coliphages as indicators of viruses & treatment effectiveness Completed

2b. Distribution Systems - Biofilm Growth and Control of Growth

 RM.M.15 - Kinetic Models for chlorine decay in distribution systems Completed H

 RM.M.16 - Enhancement of EPANET distribution system model 1998 H

 RM.M.17 - Prelim. studies of biofilm formation rates in pilot scale 1998 M

distribution systems

 RM.M.18 - Opportunistic pathogens in biofilms 2000 M

 RM.M.19 - Impact of nutrient removal on growth potential for bacteria 1999 M

 RM.M.20 - Impact of alternative treatment of biofilm growth Proposed M

 RM.M.21 - Water quality factors in distribution systems 1997 M

AWWARF Related Projects
Expected Priority

Completion

Date

2-15

Control of Bacteria in Distribution System

270 - Occurrence and control of Mycobacterium avium complex 1998

534- Fatty acid profiling for identification of environmental bacteria in Completed

distribution system

936 - Pathogens in model distribution system biofilms 1997

Minimization of Regrowth Potential

183 - Factors affecting microbial growth in distribution systems 1997

704 - Factors limiting microbial growth in distribution systems Completed

Disinfectant Residual Decay in Distribution System

261-Guidance manual for installation of booster disinfection 1998

293 - Role of pipe-water interface in DBP formation & disinfection 1997

294 - Travel times & water quality in dead ends 1997

815 - Characterization and modeling of chlorine decay Completed

NWRI Related Projects

 Interactions between pipe materials, corrosion inhibitors, biofilm Completed

Risk reduction in distribution system by on-line monitoring of pathogen ecology Completed

2c. Distribution Systems - Effect of Design and Condition on Bacterial Growth

 RM.M.22 - Water quality impacts of dead ends 1998 M

 RM.M.23 - Mixing in storage facilities 1998 M

 RM.M.24 - Alternative kinetic models for decay and DBP formation Proposed H

 RM.M.25 - Real-time monitoring systems 1999 M

AWWARF related projects

154 - Biological stability of drinking water in treatment plants and distribution 1997

systems

254 - Managing & operating finished water storage facilities 1998

260 - Water quality monitoring of distribution system. storage facilities 1998

729 - Biofilm reactor BOC measurement Completed

2d. Distrib. Systems - Effect of Treatment on Chemical/Biological Stability of Water

 R.M.M.26 - Bacterial growth in distribution systems Proposed H

 R.M.M.27 - Integrated approaches for controlling pathogens Proposed M

2e. Distrib. Systems - Maintaining Distribution System Integrity

 RM.M.32 - Evaluate primary causes of leaks/failures in distribution systems Proposed H
Expected Priority

Completion

Date

2-16

 RM.M.33 - Evaluate devices for determining structural integrity of Proposed H

distribution system

 RM.M.34 - Evaluate materials for construction of distribution system Proposed H

3a. Source Water

 RM.M.35 - Evaluate GIS for defining source water characteristics Proposed H

 RM.M.36 - Evaluate water quality models for routing point and non-point Proposed H

source water discharges

 RM.M.37 - Evaluate the impact of sudden increases in source water Proposed H

contamination on drinking water treatment
2-17

D/DBP rules

During the DBP regulatory negotiations participants were concerned with the uncertainty

in characterizing risks associated with DBPs from chlorine and alternative disinfectants. RIA

modeling indicated that the national baseline incidence of cancer attributed to chlorinated DBPs in

drinking water could range from 1 case per year (based on central tendency risk factors from

animal toxicology data for TTHMs alone) to over 10,000 cases per year (based on risk factors

suggested by a meta analysis of epidemiology studies by Morris et al). The RIA indicated that

under the Stage 1 DBP rule the national cost for avoiding one case of cancer could range from

several hundred thousand dollars to several billion dollars per year. Despite these enormous

uncertainties, the Negotiating Committee recognized that the existing risks could be large, and

therefore should be reduced. They reached a consensus that the Stage 1 requirements were of

sufficient benefit to be proposed for all system sizes, even though the costs for such a rule were

substantial. 

While no Stage 2 DBP rule could be agreed to until the benefits of such a rule became

more apparent, a possible criterion was proposed, and an RIA was conducted to understand

potential cost impacts. It was estimated that if all systems in the U.S. were required to achieve a

Stage 2 DBP rule of 40 Fg/l for TTHMs and 30 Fg/l for HAA5, without restricted use of

alternative disinfectants to chlorine (which are less expensive than precursor removal

technologies), they would incur annual costs of $1.5 billion per year above those anticipated for

Stage 1 ($1 billion per year). If systems were required to use precursor removal technologies

such as GAC and membrane technology to meet a 40/30 Fg/l Stage 2 rule, they were projected to

incur annual costs of several more billions per year than if they could meet such a standard using

alternative disinfectants to chlorine. Table 2.2 summarizes ongoing, proposed, and completed

research projects by EPA and other organizations that will provide valuable inputs to the

development of the Stage 1 and Stage 2 DBP rules. 

Stage 1 DBP Rule

As discussed previously, EPA must promulgate the Stage 1 DBP rule by November 1998. 

EPA does not envision making major changes to the 1994 proposal because it was developed

through a negotiation process and most of the public comments support the proposal. Research
2-18

from this Research Plan will be used mainly to support the development of the Stage 2 DBP rule. 

However, there are several research projects that may have an impact on the Stage 1 DBP rule. 

For health effects, a new cancer study for bromate will be available for the final Stage 1

rule (HE.D.7). This may be important because the theoretical 1 x 10 cancer risk level for -4

bromate is 0.005 mg/L while the MCL in the proposal was 0.010 mg/L. If the cancer risk from

bromate is greater than in the proposal, then there may be concern about the use of ozone as a

disinfectant. The Chemical Manufacturers Association has completed a two-generation study on

the reproductive and developmental effects of chlorite (HE.D.8). The information from this study

will be used to modify, if justified, the MCLG for chlorite and chlorine dioxide. The International

Life Science Institute (ILSI) convened an expert panel in 1996 to explore the application of the

EPA’s 1996 Proposed Guidelines for Carcinogen Risk Assessment to the available data on the

potential carcinogenicity of chloroform and dichloroacetic acid (RA.D.1). EPA is evaluating the

ILSI report and its implications for the MCLGs for chloroform and DCA. Finally, EPA is

reevaluating the available cancer epidemiology data using different meta-analytical techniques to

determine the adequacy and accuracy of the previous meta-analysis by Morris et al. (RA.D.5-6). 

The results from this research may be used in developing better estimates of the potential benefits

from the Stage 1 DBP rule. 

Additional data on the occurrence of TTHMs and HAA5 has been collected by the

American Water Works Association, the American Water Works Systems Company and several

States and has been submitted to EPA for consideration. In addition, new occurrence information

for chlorite and chlorate have been provided to EPA. This new data will be useful when

evaluating the potential regulatory impacts of the Stage 1 DBP rule.

Improvements in analytical methods will be completed in time for the Stage 1 DBP rule

for bromate (EX.D.1), haloacetic acids (EX.D.2), and TOC (EX.D.3). Research related to

improving enhanced coagulation and softening will also be completed in time for the final Stage 1

rule (RM.D.4). Many of these projects will help to better define the precursor removal

requirements in the Stage 1 DBP rule. In addition, there are several AWWARF projects that will

help to improve the analytical methods and improve DBP precursor removal (see Table 2.2) 
2-19

Stage 2 DBP Rule

The Stage 2 DBP rule is required to be completed by May 2002. In order to meet this

deadline, EPA will need to initiate a second regulatory negotiation by late 1999 to complete a

proposed rule by late 2000. EPA believes that the majority of research will be completed in time

for consideration in the final Stage 2 DBP rule. When developing the Stage 2 DBP rule, there are

several critical issues which need to be addressed in order to support the development of different

regulatory options including: 1) the magnitude of the cancer and noncancer risks (e.g.,

reproductive risks) from chlorinated waters; 2) the magnitude and relative cancer and noncancer

risks (e.g., reproductive risks) from the DBPs formed when using alternative disinfectants (e.g.,

ozone and chlorine dioxide); 3) the relative risks from brominated species versus the chlorinated

species; 4) better methods for DBPs and the collection of additional occurrence data; 5) the

evaluation of the effectiveness of GAC and membranes to remove DBP precursors; and 6) the

balancing of the risks between pathogens and DBPs.

The magnitude of the health risks from chlorinated waters and from those DBPs formed

using different disinfectants is important to understand when trying to determine "how large is

the risk" or "should we be concerned". Understanding the magnitude of the health risks from

the use of different disinfectants is critical when evaluating the different regulatory options for the

Stage 2 DBP rule and for evaluating the risk-risk tradeoffs between controlling for microbial

pathogens and DBPs. For example, using alternative disinfectants may be much more cost

effective than using advanced technologies such as membranes or GAC to comply with MCLs for

chlorinated DBPs. On the other hand, alternative disinfectants to chlorine create their own DBPs

of concern that need to be considered (e.g., bromate with the use of ozone and chlorite with the

use of chlorine dioxide). Since ozone and chlorine dioxide are more effective for inactivating

Cryptosporidium than chlorine it becomes especially important to understand the health risks of

DBPs formed using different disinfectants. 

Determining the relative risk from alternative disinfectants is important when trying to

address “do the byproducts from the use of different disinfectants present more or less of a

health risk than the byproducts from other disinfectants”. For example, systems may be

considering switching to ozone for better control of Cryptosporidium and because it forms fewer
2-20

chlorinated DBPs. The apparent major byproduct of ozonation in the presence of bromide is

bromate. If bromate presents a greater health risk than chlorinated byproducts then the switch to

ozone may actually increase the risk from DBPs. However, before these issues can be resolved it

is critical that the risks from the byproducts formed from alternative disinfectants be evaluated. 

Determining the relative risk from brominated species is important when trying to address

“do brominated species pose a greater risk than chlorinated species”. Determining the

relative risks between the brominated and chlorinated species is important because there is some

evidence that in waters with high bromide concentrations that technologies to remove DBP

precursors could increase the concentrations of certain brominated DBPs even though the group

concentrations of TTHMs and HAA5 may decrease. This may be of concern if the risks from the

brominated species are shown to present a greater health concern than the chlorinated species. 

To determine the magnitude and relative risks from the DBPs formed using different

disinfectants, information is needed on the health effects from individual DBPs or mixtures of 

DBPs along with occurrence/exposure information. In addition, information is needed on whether

the risks can most cost effectively be controlled by limiting exposure to individual DBPs and/or

surrogate parameters (e.g., TTHMs, total haloacetic acids, total organic halides [TOX], or TOC).

 If the magnitude of national cancer risk attributed to chlorinated DBPs after the Stage 1 rule is

determined to be high (e.g., greater than 5,000 cases per year), the costs for implementing a Stage

2 DBP rule, where many systems would be required to use GAC or membrane technology, may

be justified. However, if equivalent protection could be provided allowing use of alternative

disinfectants, then costs may be much lower.

During the negotiations concern was also raised as to the significance of reproductive and

developmental risks from disinfected waters. This issue is of particular importance from a

regulatory perspective. If reproductive or developmental effects are of concern, then standards

might be set to prevent the threshold risk level from occurring anywhere in the distribution system

because a single excursion above the MCL might induce illness whereas cancer risk is considered

to accrue over time. This approach to setting the MCL is unlike the existing TTHM maximum

contaminant level (MCL) or newly proposed Stage 1 MCLs for TTHMs and HAA5 (i.e., the sum
2-21

of concentrations for five haloacetic acids) where compliance is based on an annual average of

concentrations measured in the distribution system. 

Data from epidemiological and toxicology studies will be used in a weight of evidence

approach to better define the magnitude and relative of the risks for chlorinated DBPs (HE.D.1-

16 and RA.D.1-11). The epidemiology research will provide direct human information that will

reduce uncertainties in the cancer and reproductive risks from chlorinated waters, but

uncertainties will remain for the Stage 2 DBP rule (HE.D.1-6 and RA.D.5-7). The majority of

cancer epidemiology research will be completed in time for the Stage 2 rule, but the results from

newly initiated cancer epidemiology studies would probably not be available in time for

consideration for the Stage 2 DBP rule because it takes several years to design and carry out such

large studies. The toxicology research will provide substantial new information for evaluating the

cancer and reproductive risks from individual chlorinated DBPs and for evaluating the potential

for neurotoxicity and immunotoxicity (HE.D.7-12 and RA.D.1-4). Although the majority of this

research should be completed in time to be considered for the DBP Stage 2 rule, it is important to

note that the information from many of the 2-year cancer bioassays described in Chapter IV will

not be available until mid to late 2000. EPA is hopeful that preliminary results will be available

that could be used in the regulatory negotiations to provide some direction on the potential health

risks from these DBPs. Mixtures research would also provide new information to reduce the

uncertainties in the risk estimates for chlorinated waters, but this research is complex and many of

the studies, if initiated, may not be available in time for the Stage 2 DBP rule (HE.D.13-16 and

RA.D.8-10). 

Data from toxicology studies, and to a more limited extent epidemiology studies, will be

used to better define the magnitude and relative risks for DBPs formed as a consequence of using

alternative disinfectants (HE.D.1-16 and RA.D.1-11). The toxicology research will provide

information on the major DBPs formed by the use of chlorine dioxide (chlorite and chlorate),

ozone (bromate, glyoxal, formaldehyde), and possible studies on the toxicity of cyanogen chloride

(a major byproduct from the use of chloramines) (HE.D.7-12). As with the several of the

chlorinated DBPs, many of the 2-year cancer bioassays described in Chapter IV will not be

available until late 2000. There will be limited information from mixtures research on the
2-22

potential risks of DBPs from using alternative disinfectants (HE.D.13-16 and RA.D.8-10). 

Epidemiology studies may provide some information on the potential reproductive risks, but it

will be difficult to conduct cancer epidemiology studies for systems using chlorine dioxide and

ozone in the United States because of the limited historical use and small potential populations

exposed.

The EPA/NTP collaborative effort described in HE.D.7-8 will conduct cancer studies,

reproductive screening studies, and mechanistic studies for several brominated DBPs (e.g.,

bromodichloromethane, dibromoacetic acid, dibromoacetonitrile). The reproductive and

mechanistic studies should be completed in time for the Stage 2 DBP rule, but results from the

cancer studies may not be available until mid to late 2000.

For the Stage 2 DBP rule, there is a need to collect additional DBP occurrence

information and DBP precursor information to more accurately estimate the potential risks from

DBPs. It will be especially important to collect information on DBPs formed from the use of

alternative disinfectants such as ozone and chlorine dioxide. The ICR will be collecting

information on four disinfectants, 29 DBPs, five general water quality parameters (pH, alkalinity,

calcium hardness, total hardness, and ammonia), and a DBP precursor (bromide) and two

surrogates for DBP precursors (TOC, UV-254). Of the 29 DBPs, there will be four THMs, six

HAAs (3 others are optional), four acetonitriles, two haloketones, seven aldehydes, chlorate,

chlorite, bromate, chloropicrin, chloral hydrate, and cyanogen chloride. The first six months of

ICR data should be available by early 1999. In addition to collecting occurrence data for these

DBPs, it is also critical to identify new DBPs (EX.D.10) and to develop methods for non-volatile

DBPs (EX.D.11) to ensure the major DBPs have been identified. EPA believes the occurrence

data from the ICR will provide the needed information for the critical DBPs for the Stage 2 DBP

rule. 

Another important area for the Stage 2 DBP rule is the development or improvement of

analytical methods for DBPs of greatest concern. As discussed above, there are projects that are

attempting to improve the methods for bromate, HAAs, and TOC. In anticipation of the Stage 2

rule, there are research projects to improve the methods for peroxides (EX.D.7) and aldehydes
2-23

(EX.D.9). Methods for other DBPs that may be considered for the Stage 2 rule were included as

part of the ICR and are believed to be adequate for use in the Stage 2 rule (e.g., haloacetonitriles

and haloketones). Better methods may need to be developed for MX and cyanogen chloride if

they are included in the Stage 2 rule. Methods for use as precursor surrogates (TOC, SUVA, and

NOM) or DBP surrogates (TOX and TOBr) need to be developed in case these prove to be good

indicators based on information from the ICR. There is research on improving the TOC method

(EX.D.3) and to better characterize NOM (AWWARF projects). The method for TOX is

considered adequate and there is a project to improve the total organic bromide method

(AWWARF).

Another critical area for the Stage 2 rule is to determine the most cost-effective precursor

removal technologies and disinfectant application strategies that can be used to reduce the

formation of DBPs. Predicting the removal of DBP precursors and DBP formation will be based

mostly on data collected from the ICR, but also from treatment research and studies of processes

in the distribution system that affect DBP formation (RM.D.1-7; EX.D.16; RM.M.15, 16, 24,

25). In addition to EPA’s research, AWWARF is conducting a considerable amount of research

in this area (see related projects). As better design and operating parameters become available

for defining precursor removal and DBP formation, they will be used for estimating costs for

systems to achieve water quality objectives for different regulatory options. EPA believes the

majority of the treatment related research will be completed in time for the Stage 2 DBP rule.

All the information cited above will be used to assist EPA in comparing and balancing the

risk from DBPs and microbial pathogens. Current comparative risk models for drinking water

weigh the outcomes of microbial exposures to that of cancer from selected DBPs. Research

needs to be conducted on a variety of models and methods that will allow for the development of

a comparative risk assessment model which addresses multiple outcomes (e.g., cancer,

developmental, reproductive, neurotoxic effects), their impacts and costs. This research should

focus on the risk analysis and risk reduction benefits derived from minimizing exposures that

would result in adverse outcomes other than cancer. A comparative risk framework and strategic

model has been developed for DBPs and pathogens and is currently being validated and reviewed

(RA.D.11). A related project pertinent to pathogen risk assessment (RA.M.2) will provide
2-24

predictive functions concerning the magnitude of response, severity of effects, and duration of

exposure. The two projects are intended to provide a prediction of different health risk endpoints

resulting from simultaneous exposure from DBPs and pathogens. EPA intends to use these

models as part of its Regulatory Impact Analysis (RIA) for evaluating different

LT2ESWTR/Stage 2 DBP combined regulatory options.
2-25

TABLE 2.2: RESEARCH TO SUPPORT THE DBP RULES

Expected Priority

Completion

Date

A. HEALTH EFFECTS RESEARCH

1. Epidemiology - Development/Application of Improved Tools for Field Research

 HE.D.1- Improving estimates of residential DBP exposure in epi .studies. 1997 H

 HE.D.2- Improving measures of biologic effect: evaluation of biomarkers 2000 H

 HE.D.3-Improving methods for managing health and exposure data 1998 H

2. Epidemiology - Feasibility/Full Scale Studies

 HE.D.4 - Feasibility studies: Cancer (Research Council) 1998 H

 HE.D.5 - Feasibility studies: Reproductive effect (Research Council) 1998 H

 HE.D.6 - Full scale studies; Cancer and reproductive effects

 - Cancer Proposed if

feasible

H

 - Reproductive effects Proposed if

feasible

H

3. Toxicology - Hazard Identification and Dose-Response

 HE.D.7 - Cancer dose-response studies 2000 H

 HE.D.8 - Reproductive/developmental effects screening studies 2000 H

 HE.D.9 - Neurotoxicity studies 2000 M

 HE.D.10 - Immunotoxicity studies 2000 M

AWWARF Related Projects

738 - Dose-response relationship of DCA & TCA-induced proliferation Completed

 CMA: Chlorite/Chlorine Dioxide 2 generation reproductive study 1997

4. Toxicology - Pharmacokinetic and Mechanisms of Action

 HE.D.11 - Pharmacokinetic and mechanistic research - cancer 2000 H

 HE.D.12 - Pharmacokinetic and mechanistic research - reproductive 2000 H

AWWARF Related Projects

432 - Mechanistic basis and relevance of rat kidney tumor formation Completed

617 - Carcinogenic mechanisms in rat & mouse hepatocytes 1997

701 - Induced hepatic tumors with induction of peroxisomes 1997

5. Toxicology - DBP Mixtures
Expected Priority

Completion

Date

2-26

 HE.D.13 - Mixtures feasibility study 2000 H

 HE.D.14 - Toxicologic evaluation of drinking water mixtures Proposed if

feasible

H

 HE.D.15 - Studies of DBP interactions 2000 M

 HE.D.16 - Mutagenicity screening studies of drinking water mixtures 2001 H

B. EXPOSURE RESEARCH

1a. DBP Methods - Stage 1 DBP Rule

 EX.D.1 - Low level bromate measurement 1999 H

 EX.D.2 - Improved method for haloacetic acids Completed H

 EX.D.3 - Expand quality control for TOC, evaluate new TOC methods 1998 H

 EX.D.4 - Low level ClO2 measurement (depends on health data) Proposed M

 EX.D.5 - Real-time monitoring for disinfectant residuals Proposed L

 EX.D.6 - PE studies for DBPs and disinfectants Ongoing H

AWWARF Related Projects

159 - Improved methods for isolation and characterization of NOM 1997

163 - Development of improved method for haloacetic acids 1997

 417- Development of fiber optic chemical sensors for monitoring organic Completed

compounds (TOC)

830 - Bromide-ozone interactions (incl. develop analytical technique for total Completed

organic bromide)

1b. DBP Methods - Stage 2 DBP Rule and Longer-Term

 EX.D.7 - Methods for peroxides 2000 M

 EX.D.8 - Real-time, in-plant monitoring of DBPs 1999 M

 EX.D.9 - Improved method for aldehydes 1998 M

2a. DBP Exposure - DBPs from Different Disinfectant Combinations

 EX.D.10 - Identify new DBPs from alternate disinfectants 2000 H

 EX.D.11 - Methods for non-volatile DBPs 2000 H

AWWARF Related Projects

825 - Bromide Survey Completed

2b. DBP Exposure - Factors that Affect Exposure Levels and Human Exposures

 EX.D.12 - DBP changes in distribution system Proposed M
Expected Priority

Completion

Date

2-27

 EX.D.13 - DBP interactions w/foods and associations w/dietary intake 2000 M

 EX.D.14 - Exposure to DBPs through showering Proposed M

 EX.D.15 - Markers of DBP exposure Proposed M

 EX.D.16 - Models of DBP exposure 2000 H

 EX.D.17 - Exposure as function of population distribution Proposed M

 EX.D.18 - Tapwater consumption 1997 H

C. RISK ASSESSMENT RESEARCH

1. Characterizing Risk of Individual DBPs

 RA.D.1 - Cancer risk assessments 2000 H

 RA.D.2 - Cancer combination study for bromates 1997 H

 RA.D.3 - Noncancer risk assessments 2000 H

 RA.D.4 - Risk characterization 2000 H

2. Characterizing Risks from Chlorinated Waters

 RA.D.5- Evaluate newer epidemiologic studies 1998 H

 RA.D.6- Assessment of previously conducted studies 1998 H

 RA.D.7 - Identify on going cancer studies 1998 H

3. Methods and Models to Characterize Risks from Mixtures

 RA.D.8 - Characterization of interactions for mixtures of DBPs. 1998 M

 RA.D.9 -Threshold studies for D/DBPs 1998 H

 RA.D.10 - Use of QSAR model to estimate risk for single cmpnds/classes of 1997 H

compounds within a mixture

4. Methods and Models to Compare Risks

 R.A.D.11 - Comparative Risk Analysis 2000 H

D. RISK MANAGEMENT

1. Effectiveness of Treatment Processes in Reducing DBP Precursors

 RM.D.1 - Enhanced softening for precursor and pathogen removal 2000 H

 RM.D.2 - Effects of ozone & biofiltration for control of precursor and pathogens

 a. - Control precursor, pathogen and pesticide removal 1998 H

 b - Effect of pH on ozonation and enhanced coagulation 2000 H

 RM.D.3 - Analyze ICR data from GAC, membrane bench and pilot studies 1999 H
Expected Priority

Completion

Date

2-28

 RM.D.4 - Removal of DBP precursors by GAC and membranes Completed H

 RM.D.5 - Membrane scale-up and fouling 1998 M

AWWARF Related Projects

DBP Precursor Control - GAC

816 - Removal of DBP precursors by GAC adsorption 1997

DBP Precursor Control - Coagulation

531 - Humic acid removal using ferric chloride Completed

814 - Removal of DBP precursors by optimal coag. & and precip. softening 1997

934 - Optimizing Ozonation for turbidity. & Organics removal Completed

DBP Precursor Control - Oxidation and Biological Filtration

252 - Optimizing filtration in biological filters 1998

289 - Advanced oxidation and biodegradation processes 1998

631 - Removal of natural organic matter in biofilters Completed

712 - Design of biological processes for organics control 1997

DBP Precursor Control - Membrane Technology Issues

170 - Reverse osmosis and nanofiltration for organics removal 1997

264 - Integrated membrane systems to control microbes/ DBP precursors 1999

601 - Ultrafiltration membrane pretreatment and nanofiltration Completed

826 - Membrane technology for drinking water - Joint Report 1997

904 - Biofouling in membrane processes 1997

Other Issues

271 - Improving clearwell design for DBP and CT compliance 1998

361 - Case studies of impacts of treatment changes on biostability on full-scale 1999

distrib. systems

369 - Case studies of modifications of treatment practices to meet the new 1999

D/DBP regulation

2. Effectiveness of Alternative Disinfectants in Limiting DBP Formation

 RM.D.6 - Ozone by-product formation and control 1999 H

AWWARF Related Projects

Formation and Control of Ozonation Byproducts

156 - Strategies to control bromide and bromate ion 1997

504 - Ozone & biological treatment for DBP control and biological stability Completed

525 - Evaluation of PEROXONE advanced oxidation process 1997

533 - Effect of carbonate/bicarbonate alkalinity on advanced oxidation processes Completed

709 - Impacts of ozonation on formation of chlorinated DBPs. 1997

830 - Bromide-ozone interaction in water treatment Completed
Expected Priority

Completion

Date

2-29

832 - Reaction of ozone and hydroxyl radicals with amino acids Completed

Formation and Control of Chloramine DBPs

710 - Nitrification occurrence and control in chloraminated water systems Completed

803 - Factors affecting DBP formation during chloramination 1997

937 - Chloramine decomposition kinetics and degradation products. 1997

Formation and Control of Chlorine Dioxide related DBPs

611 - Sources, occurrence, & control of ClO2 byproduct residuals in drinking Completed

water

833 - Minimizing chlorate ion formation in drinking water when hypochlorite Completed

used

3. Small Systems Technology for Precursor and DBP Control

 RM.D.7 - Membranes/advanced oxidation/other technology combinations 1999 H
2-30

Ground Water Disinfection Rule

The 1996 SDWA amendments require EPA to promulgate drinking water standards for

ground water no sooner than August 1999 and no later than May 2002. EPA plans to propose a

groundwater rule in January 1999 and finalize the rule in November 2000 in conjunction with the

LT1ESWTR. 

 

Under the negotiated rule-making for DBPs, it was assumed that the GWDR would

prevent increases in microbial risk while ground water systems using disinfection complied with

the Stage 1 DBP rule. Ground water systems not required to disinfect would avoid risks from

DBPs and not be required to comply with DBP regulations. Also, ground water systems

required to disinfect but serving only transient populations (most non-community systems) would

not be subject to DBP standards unless risks from short-term exposure were determined to be of

concern. 

While some general problems are common to all drinking water systems and can be

adequately addressed by research developed for the surface water and DBP rules, a distinct set of

conditions and assumptions apply to contamination and treatment of ground waters that must be

considered. Key regulatory issues include: 1) whether practical criteria can be determined for

when systems can avoid disinfection while still providing a safe water; 2) what level(s) of

disinfection to require for systems which are vulnerable to fecal contamination in the source

water; and 3) what control measures to require to limit contamination to the distribution system. 

Approaches being considered for addressing the above issues include: 1) basing regulatory

criteria on their ability to ensure that a systems is below a desired risk level (e.g., less than a 10-4

annual rate of infection from most viruses), taking cost into consideration; 2) requiring

disinfection to reduce risks from viruses to the extent that is technically and economically feasible

for most systems, while allowing systems that are clearly not vulnerable to fecal contamination to

avoid disinfection (e.g., based on occurrence of indicators such as coliforms and/or coliphage, and

minimum set-back distances based on hydro geological features); and 3) same as (2) but only

requiring systems to disinfect that are clearly vulnerable to fecal contamination (e.g., based on

occurrence of coliforms and/or coliphage). 
2-31

Given the potential occurrence of over 100 enteric viruses in drinking water, the risk

based approach can only practically be pursued by focusing on those viruses which occur most

frequently and at the highest levels in drinking waters, are most resistant to ambient stress and

treatment, and are clinically most significant. Ideally, EPA would predict a minimum level of

treatment or set-back distance (at a particular site) for virus "A" to ensure that there are less than

a fixed rate of infection (e.g., 1 infection per 10,000 people per year) from the viruses "A", "B",

"C", and "D" etc. The problems of developing such an approach are numerous including viruses

that behave differently in their die-off and transport through the ground; disinfectants with varying

degrees of effectiveness for inactivating different viruses; and viruses that occur at different

concentrations with variability in source waters and upon infection produce a wide range of

different clinical manifestations, ranging from no symptomatic response or mild gastroenteritis to

hepatitis and possibly death. 

Model development of this approach is further hampered by the wide range of

uncertainties for aquifer hydrogeological characteristics and fate and transport properties of the

various pathogens and indicator organisms. These difficulties have led to a two-pronged

approach for research supporting a GWDR. One prong is to consider the uncertainties and

unknowns for the various elements in these models to determine 1) if they can be reduced such

that meaningful predictions are fundamentally possible, and 2) if the model predictions can be

validated in the field. The other prong is to focus on other approaches to estimating groundwater

vulnerability, primarily considering occurrence data and traditional well site selection criteria, such

as set back distances, confining layers, land uses, well depth, etc. These need to be likewise

considered for their ability to meaningfully predict vulnerability/non-vulnerability.

The GWDR will affect a fundamentally different class of public water supply systems than

the ESWTR. The 10,000 or so surface water systems include a substantial fraction of large

community systems with substantial infrastructure and economic resources. The 160,000

groundwater systems are almost exclusively very small non-community and community systems

with limited resources and infrastructure. The regulatory realities require that EPA consider

simple, feasible assessment, treatment and monitoring approaches.
2-32

EPA is considering developing the RIA using three regulatory approaches described

above. However, before these approaches can be used additional information is needed as

described below.

Table 2.3 summarizes completed, ongoing and proposed research to help define the

significance of the public health problem in ground water systems. These projects include

information on known and estimated disease (outbreaks and endemic disease rates), microbial

pathogen and indicator occurrence in source waters and distribution systems, and exposure risks

associated with various contamination sources (HE.M.5, 6, 9, and 10; EX.M.8, 10 and 14 -18;

RA.M.1-3). This information will indicate the nature and scope of the public health problem and

allow for estimates of the baseline risk level from which to base the RIA and develop appropriate

regulatory goals. Surveys on disinfection practice by industry will help characterize types and

levels of disinfection treatment currently practiced by groundwater systems. 

Strategies to determine system vulnerability to microbial contamination and criteria to

avoid disinfection have to be developed and field tested. Information on factors affecting and

limiting microbial contamination of groundwater will help establish criteria for avoiding

disinfection. Such information includes physical and chemical properties governing fate and

transport of microbes in the subsurface, site-specific factors such as land use patterns, and

hydrogeological properties affecting vulnerability (EX.M.23-26). 

UV disinfection research is targeted because it may be the least costly technology for

many small systems to adequately treat for viruses, especially non community systems (i.e., those

not having a distribution system), or multiple-well systems (RM.M.9 and RM.M.13). Also,

systems using UV disinfection would likely avoid formation of DBPs of any health risk

significance. 

Approaches for monitoring to ensure public protection from waterborne viruses as well as

bacteria may include coliphage and are being investigated (see related projects).
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TABLE 2.3: RESEARCH TO SUPPORT THE GROUND WATER DISINFECTION RULE

Expected Priority

Completion

Date

A. HEALTH EFFECTS RESEARCH

1. Health Research on Waterborne Pathogens

 HE.M.5 - Infectious dose of Norwalk virus 2000 H

 HE.M.6 - Infectious dose of other priority pathogens Proposed M

 HE.M.9- Investigations of waterborne disease outbreaks Ongoing H

 HE.M.10 - Surveillance tool for waterborne disease outbreaks Completed H

AWWARF Related Projects

268 - Fingerprinting techniques for opportunistic pathogens & illness 98

B. EXPOSURE RESEARCH

1b. Microbial Methods - Viruses 

 EX.M.8 - Application of PCR technologies & gene probes to detect 1999 M

viruses in water

 EX.M.9 - Norwalk virus 2000 H

 EX.M.10a - Methods for emerging viruses Proposed H

 EX.M.10b - PCR based detection of viruses in water 1997 H

AWWARF Related Projects

292 - Rapid PCR-based monitoring of entero viruses 1998

429 - Male-specific coliphages as indicators of viruses Completed

612 - Analysis of viruses by gene probe Completed

726 - Viral and microbial methods for groundwater 1997

916 -PCR Technologies for Virus Detection in Groundwater 1997

2a. Microbial Exposure - Pathogen Occurrence

 EX.M.14 - Occurrence of Mycobacterium 1998 H

 EX.M.15 - Occurrence of heterotrophic bacteria with virulence 2001 H

characteristic

 EX.M.16 - PCR method for Legionella Completed L

 EX.M.17 - Pathogenicity of heterotrophic bacteria found in drinking 1998 H

water.

 EX.M.18 - Occurrence of opportunistic pathogens in biofilms Proposed M

AWWARF Related Projects

186 - Survey viruses in ground waters Completed
Expected Priority

Completion

Date

2-34

3a. Groundwater - Survival and Transport in the Subsurface

 EX.M.23 - Virus survival in the subsurface 2000 H

 EX.M.24 - Virus transport in the subsurface 2000 H

AWWARF Related Projects

262 - Field study of virus and indicator transport in ground water 98

3a. Groundwater - Methods for Protecting Wells and Springs

 EX.M.25 - Viral transport and fate models 2000 M

 EX.M.26 - Vulnerability of ground-water to pathogens 2000 H

 EX.M.27 - Delineation of natural protection zones 1998 M

 EX.M.28 - Vulnerability & Sensitivity Analysis 1998 H

 EX.M.29 - Occurrence of Clostridium perfringens 1997 H

 EX.M.30 - Aquifer well mapping Completed M

 EX.M.31 - Correlation of water age and microbial viability H

 EX.M.32 - Septic Tank Siting 1999 H

 EX.M.33 - Virus Sampling and Phage Research 1997 H

C. RISK ASSESSMENT RESEARCH

1. Risks from pathogens

 RA.M.1 - Devel. compre. micro risk assess paradigm for water 2000 H

 RA.M.2 - Evaluation/Application of various dose-response models 1998 H

 RA.M.3 - Evaluation and application of methods to assess risk associated 2000 M

with exposures to multiple pathogens, routes, and durations

D. RISK MANAGEMENT RESEARCH

 R.M.M.9 - UV disinfection efficiencies for Norwalk viruses Proposed H

RM.M.30 - Evaluate alternative inactivation processes for controlling Proposed H

viruses

AWWARF Related Projects

180 - UV inactivation of viruses in natural waters 1997

353 - Inactivation rates of viruses and bacteria in saturated and unsatured 1999

subsurface media

702 - Development and validation of rational design methods of disinfection Completed

809 - By-products of UV treatment of groundwater Completed

817 - Membrane filtration techniques for microbial removal Completed
Expected Priority

Completion

Date

2-35

NWRI Projects:

 Deposition mechanisms and long-time scale factors influencing virus Completed

transport in porous media

 Groundwater Transport of Viruses Completed

 Field experiment and modeling of vira transport in groundwater Completed

 Transport and fate of viruses in the vicinity of pumping wells Completed
3-1

 CHAPTER III. RESEARCH FOR MICROBIAL PATHOGENS

A. BACKGROUND

Waterborne infectious disease outbreaks have been attributed to a variety of pathogenic

bacteria, parasites and viruses. Giardia has been responsible for about half of the outbreaks of

disease where the causative agent was identified. Cryptosporidium outbreaks have been reported

less frequently, but the number of cases associated with the outbreak have been much larger. 

Since 1991, the percent of outbreaks attributable to Cryptosporidium has doubled. In 1993 -

1994 reporting period, about 17% of all reported outbreaks were caused by Cryptosporidium. 

Many outbreaks of acute gastrointestinal illness have not been linked to specific pathogens. 

Viruses are thought to be the cause of a large portion of the outbreaks where the agent is not

identified. Establishing the association between water ingestion and illness is difficult because of

our inability to culture many of the viruses. In addition to reported outbreaks where the cause is

unidentified, it is likely that many outbreaks occur that are either unrecognized or unreported. 

Furthermore, if it is determined through further research that endemic microbial disease is a real

occurrence (as suggested by studies in Canada), public health concern over waterborne pathogens

would increase significantly.

The sources of pathogenic microbes in drinking water associated with disease are usually

related to fecal matter from warm-blooded animals and humans. Humans are the main source of

pathogens, but animals are frequently implicated as in the outbreaks caused by Giardia and

Cryptosporidium. Another source of potential pathogens is the water distribution system and its

associated storage facilities. Breaks in the integrity of the distribution system can allow the

introduction of pathogens. In addition, many bacteria can grow and persist in the distribution

system, and some of them (e.g., Mycobacteria and Aeromonas) can cause infections and disease

under certain conditions. The conditions are not well defined, but they can include a host whose

natural defense barriers have been compromised, an organism that has the ability to take

advantage of the opportunity presented by a compromised host, and an environment that is

conducive to the growth of the pathogen.
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This chapter describes proposed research for microbial pathogens in the areas of health

effects, exposure, risk assessment, and risk management. The major research questions in each

area are summarized in Table III-1. For each question, the state of the science, research needs

and proposed research projects are described.

Table III-1 - Major Research Questions for Microbial Pathogens

Health Effects

1. What are the major pathogens of public health concern?

2. What is the nature and magnitude of disease associated with exposure to these

waterborne agents?

Exposure

1. What methods are needed to adequately measure or estimate occurrence of

pathogens in drinking water?

2. What are the frequencies of occurrence and densities of pathogens in source water, 

finished water, and distribution systems, and what is the population distribution of

exposures to pathogens?

3. What are the factors affecting microbial contamination of ground water?

Risk Assessment

1. How can the risks posed by pathogens in drinking water be characterized? 

Risk Management

1. How effective are various treatment processes in removing pathogens? 

2. How can the quality of treated water be maintained in distribution systems?

3. How can source water be protected to ensure that it is consistent with finished

water quality of acceptable microbial risk after appropriate treatment?
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B. HEALTH EFFECTS RESEARCH

1. What are the major pathogens of public health concern?

2. What is the nature and magnitude of disease associated with exposure to these

waterborne agents?

State of the Science

 

The continued occurrence of waterborne disease outbreaks in the U.S. and questions in

the scientific community about the adequacy of conventional water treatment in preventing

endemic waterborne disease highlight the need for research to evaluate the impact of water quality

and type of treatment process on the occurrence of waterborne disease. A critical public health

issue relates to the need to identify and characterize pathogens that may pose increased risks of

infection and disease in the general population, as well as in susceptible populations such as the

immuno compromised, elderly or infants.

As discussed earlier, a variety of pathogenic bacteria, viruses and parasites are still

considered to pose serious public health risks when treatment is inadequate. In general, the health

risks associated with exposure to these agents in drinking water are poorly characterized. The

known source water contaminants of greatest concern include the protozoan parasites

Cryptosporidium and Giardia, and the enteric viruses hepatitis A and Norwalk virus. "Emerging"

pathogens about which relatively little is known but which could be important public health

concerns under certain conditions include Microsporidium, Cyclosporidium, hepatitis E, and

Helicobacter pylori. Opportunistic or conditional organisms are those that must be amplified in

the environment and then come into contact with a host that is susceptible to disease. Examples

of these types of organisms are Legionella and Mycobacterium. Research is needed to

characterize the magnitude of the risk caused by these organisms in susceptible populations and to

more carefully describe the risk factors for susceptibility.
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Characterizing microbial health risks requires knowledge of a number of important

pathogen- and host-specific factors. Reliable information on the infectious dose of these agents is

necessary for quantitative risk assessments, yet such data are either limited or unavailable for most

important waterborne pathogens. A need also exists to better characterize the virulence of these

agents, the range of responses to infection, and the influence of host factors (e.g., immune status)

on the course of infection and disease. Understanding the virulence characteristics of pathogenic

and opportunistic microorganisms is important for estimating the likelihood that infections will

lead to disease in healthy and compromised individuals. Humans exposed to pathogens may in

some cases be asymptomatic or may experience mild to severe effects. Although gastrointestinal

symptoms are most commonly observed, other disease symptoms or states (e.g., cardiovascular,

respiratory, liver, and central nervous system effects) may also be induced by certain pathogens. 

Finally, secondary spread of disease is an important but poorly quantified factor that should

investigated.

Cryptosporidium is known to cause an acute, self-limiting disease in immunocompetent

persons. Infections in immunocompromised individuals generally cause a more chronic, severe

disease for which no safe and effective form of treatment is available. Additional health research

on Cryptosporidium is needed to permit a more comprehensive characterization of the important

pathogen- and host-specific factors described above. Some data on the infectious dose of Giardia

are available, and additional research on this protozoan is considered to be a lower priority than

Cryptosporidium at the present time since Cryptosporidium appears to be more resistant to

disinfection. Very little is known about the pathogenicity of the enteric viruses, which are

believed to be responsible for a significant portion of the outbreaks for which the causative agent

was not identified. A continuing investigation of the infectious dose of Norwalk virus should

provide important information to help characterize the risk posed by this agent. Important data

gaps exist for hepatitis A virus, but research in humans is problematic because of its highly

pathogenic nature. As current studies resolve critical issues for priority pathogens such as

Cryptosporidium and Norwalk virus, efforts will shift to emerging pathogens. Clearly, the list of

known and emerging pathogens for which major data gaps exist is extensive and growing, and

prioritization of these agents for further study will be an ongoing effort as new information on

exposure and health concerns becomes available.
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Epidemiology studies of both endemic waterborne disease and epidemic events (i.e.

outbreaks) can be highly useful in characterizing the magnitude of microbial risks, identifying

etiologic agents, characterizing the health effects associated with a variety of different pre- and

post-treatment contamination problems, evaluating differences in susceptibilities of different

populations to pathogens, and validating risk models. These studies can also help to identify

important research needs in the areas of health effects, exposure, risk assessment and engineering. 

Exposure research on known opportunistic and "emerging" waterborne pathogens should be

linked with health research in the laboratory and field to permit a determination of the public

health importance of finding these agents in water supplies. Better surveillance tools are needed

to enable public health officials and scientists detect and respond more quickly when waterborne

disease is first identified in a community.

The existing epidemiologic data base is inadequate for determining the nature and

magnitude of endemic and epidemic waterborne disease in the U.S. A limited number of followup studies of the most significant outbreaks have been conducted. The results of two recent

studies of endemic waterborne disease in Canada indicated that there was an excess risk of

gastrointestinal illness of 15% to 35% in the study groups that consume water treated by

conventional techniques. As described below, the EPA has initiated epidemiology studies to

further address the issue in U.S. populations, and additional studies are being planned through a

collaborative effort between EPA and the Center for Disease Control (CDC). The EPA and CDC

are also working together to develop a biannual report on waterborne disease outbreaks. Finally,

the EPA is developing improved estimates of annual incidence of endemic waterborne disease in

the U.S., using more recent pathogen occurrence data and improving estimates of exposure and

health effects.

Research Topics and Priorities

a. Pathobiology of infection and disease for the most important waterborne pathogens

Research on the pathobiology of infection and disease includes studies to describe doseresponse relationships, characterize pathogen virulence and the range of outcomes of infection,
3-6

and evaluate the impact of host immune status on infection and disease. Two approaches for

obtaining this information include highly controlled clinical studies in humans and laboratory

research in animals. Epidemiology studies, which are described in section (b), are also very

effective tools for characterizing infections and the factors that influence disease outcomes.

Nearly all of the health effects research on microbial pathogens was assigned a high

priority because it addresses high risk, high uncertainty issues of considerable regulatory

importance. The 1996 SDWA Amendments specifically require EPA to conduct the types of

research described below, including dose-response studies on pathogens such as Cryptosporidium

and Norwalk virus, and studies of the factors that influence these relationships in susceptible

populations. If individuals exhibit significant immune response to Cryptosporidium (project

HE.M.1), if the current high-to-low dose extrapolation of risk is not appropriate (project

HE.M.2), or if oocyst strain infectivity (project HE.M.3) in immunocompetent individuals varies

significantly, then these factors would greatly affect the overall risk assessment. From a costbenefit perspective, research that better defines the dose-response curve and its significant

associated uncertainties for the most important waterborne pathogens is a high priority, because

of the high and possibly exponentially increasing costs of treating water to decrease the

concentration of viable cysts to lower and lower levels. Over-predicting the risk could have

dramatic cost implications as well as cause utilities to change to alternate disinfectants such as

ozone. Project HE.M.4 was ranked high because it addresses the critical risk assessment issue of

variations in susceptibility to Cryptosporidium, and it could affect the EPA/CDC guidance to

severely immunocompromised persons. The Norwalk infectious dose study (project HE.M.5) is

also a high priority because of its potential impact on the risk assessment for groundwater

systems. As laboratory techniques to identify and characterize pathogenic or toxigenic

microorganisms improve, and as current research activities resolve critical uncertainties for

Cryptosporidium and Norwalk virus, priorities for research on other pathogens such as those

considered in project HE.M.6 would increase from medium to high.

HE.M.1 - Infectious dose of Cryptosporidium Infectious dose study in groups of

immunocompetent volunteers with and without preexisting antibodies to this protozoan,

with rechallenge of the latter group of volunteers one year after initial exposure.
3-7

Priority: High

HE.M.2 - Validity of the dose-response model for Cryptosporidium using low

challenge doses in test animals Dose-response study in mice to evaluate the suitability

of the low dose extrapolation approach used in the existing model.

Priority: High

HE.M.3 - Cryptosporidium virulence study using different strains Identify, collect

and propagate in calves four isolates of C. parvum from geographically diverse sites,

identify molecular or biochemical markers of virulence, and ultimately establish doseresponses in humans for two of the new isolates.

Priority: High

HE.M.4 - Cryptosporidium infectious dose in normal and immuno compromised

animals Determine and compare the infectious dose of oocysts in immunocompetent and

immunocompromised juvenile and adult guinea pigs.

Priority: High

HE.M.5 - Infectious dose of Norwalk virus Second phase of an EPA-funded infectious

dose study in humans to further characterize the dose-response and the influence of hostspecific factors (such as immune status) on infection and disease. The first phase will be

complete in 1997, and the second phase will end in 2000. 

Priority: High

HE.M.6 - Infectious dose of other priority pathogens (to be determined)

Studies of pathogens such as rotavirus, opportunistic bacteria, or emerging pathogens, to

be prioritized upon further consideration of needs.

Priority: Medium 

b. Characterization of epidemic and endemic waterborne disease
3-8

Research described in this section includes community-based epidemiology studies to

characterize endemic as well as epidemic waterborne infectious diseases. A major area of interest

is the microbial health risks associated with the use of different drinking water treatment

techniques (particularly filtration vs. no filtration). An important aspect of this research is to

develop better tools to assess exposure to waterborne pathogens in epidemiology or surveillance

studies, and to facilitate early detection of outbreaks when they occur. The projects described

below, like those identified above, are considered high priority because they fulfill the top three

criteria of addressing high risk, high uncertainty issues that have significant regulatory impact. 

These efforts will lead to a better understanding of the magnitude of endemic and epidemic

waterborne disease, and of the factors that contribute to their occurrence. Better sensitivity in

epidemiological studies will allow for improved validation of dose-response predictions from

existing/newly developed dose-response curves. The projects listed below are considered a high

priority because they are expected to narrow the uncertainty in risk estimates for Cryptosporidium

and for other priority pathogens as well. Furthermore, the 1996 SDWA Amendments require

EPA and CDC to jointly conduct waterborne disease occurrence studies for at least five major

U.S. communities or public water systems, and to develop a national estimate of waterborne

disease occurrence.

HE.M.7 - Characterization of endemic disease: Health effects associated with

differences in source water quality and treatment process This includes epidemiologic

research to evaluate the impact of different treatment strategies on reducing endemic

waterborne disease. This effort should be linked to exposure research involving the

identification of new pathogens and the development of field detection techniques, as well

as to risk management and assessment research activities. This research should also

provide opportunities for studying subpopulations that may be highly susceptible to

waterborne infectious disease. Both surface and ground water sources of varying water

quality should be considered for study. In an ongoing, phased effort, potential study sites

in several communities have been identified where treatment changes are planned, and the

health status of selected communities before and after these changes will be determined. 

The EPA/CDC waterborne disease occurrence studies required by the 1996 SDWA

Amendments have also been initiated in 1997. To the extent possible, these studies will
3-9

include efforts to identify the etiology of waterborne illnesses that are reported.

Priority: High

HE.M.8 - Immunological assays for assessing exposure in epidemiology studies

Development or improvement of immunological tools to determine the presence of

antibodies to important waterborne pathogens, and application of these tools in

community-based studies. This research explores the possibility that serological tools may

be useful tools for assessing exposure to important waterborne pathogens. An ongoing

phased study is evaluating the use of serosurveys as a tool for assessing exposure to

Cryptosporidium. After completing the feasibility phase to more fully evaluate the

usefulness of this technique, full-scale studies in several cities may be conducted. 

Concurrent with this effort is a study to evaluate the ability of the ELISA technique to

measure Cryptosporidium antibodies in human sera.

Priority: High

HE.M.9 - Investigations of waterborne disease outbreaks Rapid deployment of EPA

scientists with appropriate expertise in health, exposure and control technology to conduct

epidemiologic investigations of outbreaks as they occur. This would greatly enhance the

opportunity to characterize the microorganism(s) responsible for the outbreak, the host

factors that influence infection and disease (including the identification of susceptible

subpopulations), and the status of the treatment process prior to and during the outbreak. 

This would be a joint initiative with the CDC, and would involve appropriate state and

local agency personnel.

Priority: High

HE.M.10 - Surveillance tools for waterborne disease outbreaks Development of tools

or mechanisms of surveillance to improve the recognition and subsequent investigation of

waterborne disease in communities. An ongoing study is evaluating the feasibility of using

anti-diarrheal drug sales as a surveillance tool for waterborne disease outbreaks.

Priority: High
3-10

C. EXPOSURE RESEARCH

1. What methods are needed to adequately measure or estimate occurrence of pathogens

in drinking water?

State of the Science

Methods for measuring some of the important pathogens associated with waterborne

infectious disease are either nonexistent or not effective because they are too inaccurate and

imprecise. In either case, these shortcomings have produced great uncertainty with respect to

exposure assessments, which has hindered the establishment of sound regulations for drinking

water quality and led to the use of many assumptions in characterizing risks associated with

drinking water.

Giardia and Cryptosporidium usually occur in very low densities in source water and

finished drinking water. This characteristic necessitates sampling large volumes of water,

sometimes up to 1000 liters, through a filter. This and subsequent steps in the currently available

method may contribute to its inaccurate and imprecise nature. A major issue is that only a small

fraction of the total sample volume collected can be feasibly analyzed; low-percent recoveries and

poor precision are difficult to avoid. The current procedures are being evaluated and improved by

EPA scientists and other researchers. New methodology, such as the gene probe polymerase

chain reaction method, is being developed and will become available for evaluation at some time

in the future.

Some methodology is available for measuring waterborne viral pathogens such as the

enteric viruses, rotavirus and hepatitis A virus. In the case of the latter two viruses, the methods

for their detection and quantification are time-consuming and non-facile. Norwalk virus has been

associated with many waterborne outbreaks as shown by seroepidemiology. This virus, however,

cannot yet be grown in tissue culture. This lack of a suitable method for detecting and measuring

this viral pathogen has limited the conduct of exposure assessments and meaningful effects

assessments.

Some of the newly emerging pathogens associated with water cannot be efficiently
3-11

measured in water samples because suitable methods are not available. Two examples of

pathogenic protozoa for which monitoring methods do not exist are Cyclospora and

microsporidia. Methods for these parasites should be developed and evaluated in anticipation of

the future need to measure these pathogens. Similarly, the waterborne pathogen Mycobacterium

avium cannot be easily measured because the available methods have been developed for testing

clinical samples. The same can be said for Helicobacter pylori, another potential waterborne

pathogen that has been associated with cases of gastric ulcers and stomach cancer in humans. 

Pathogens may be present in tap water due to inadequate disinfection or may enter faulty

distribution systems post treatment. Due to the acute nature of most microbial diseases, real-time

continuous monitoring techniques are needed to detect the possible presence of pathogens in

distribution systems and to provide timely advice to water consumers.

Research Topics and Priorities

a. Methods for detecting and enumerating Cryptosporidium and Giardia (including

identifying the viability potential) in source and finished drinking water, and methods for

other emerging protozoa

Cryptosporidium is emphasized because of the great attention placed on the organism due

to recent outbreaks and its resistance to inactivation by chlorine. This protozoan may become the

focal organism for drinking water regulations. Research that is expected to result in improved

methods for detecting Cryptosporidium or in a method for detecting viable oocysts has generally

been assigned a high priority. These projects are expected to improve EPA's ability to estimate

occurrence and exposure. Project EX.M.4 was assigned as medium priority because this

methodology will not provide means of determining viability or infectivity of cysts or oocysts.

EX.M.1- Immunological techniques for protozoa Conduct research to examine and

improve immunological techniques for detecting Cryptosporidium, and other pathogenic

protozoa. Practical, improved technology will enhance the isolation, identification and

quantification of pathogenic protozoa. 

Priority: High 

EX.M.2 - Gene probes for detection of viable Cryptosporidium oocysts Develop
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probes to mRNA and other nucleic acids, and examine their potential as viability markers

for pathogenic protozoan cysts and oocysts. 

Priority: High

EX.M.3 - Cultural method for Cryptosporidium in environmental samples

Develop a cultural method for detecting Cryptosporidium in environmental water samples. 

The objective is to develop and evaluate a tissue culture assay for oocysts. 

Priority: High 

EX.M.4 - PCR methods for Giardia and Cryptosporidium Develop polymerase chain

reaction (PCR) methods for Giardia and Cryptosporidium in environmental samples. 

Methods will be investigated for recovering protozoa nucleic acids directly from water

samples. 

Priority: Medium

EX.M.5 - Protozoa methodology protocol development workshop

(Ongoing) This workshop will produce protocols for developing and evaluating a new

method; for comparing methods; and for determining the equivalency of procedures,

reagents and materials within a method. It also will develop recommendations on sample

volume for raw waters to be included in a comparison survey. 

Priority: High

EX.M.6 - Comparison of methods for Giardia and Cryptosporidium in water

Comparison of the best available methods for detecting and quantifying cysts and oocysts

through multi-lab evaluation using water samples from multiple sites, using criteria

developed in project EX.M.5. 

Priority: High

EX.M.7 - New protozoa agents Develop methods to identify new potential protozoan

pathogens in drinking water such as Cyclospora or Microsporidia. The objective of this

research is to develop procedures, either in vitro or in vivo, for producing stocks of these

potential pathogens. Methods for detection and identification will be developed and

evaluated using the stock organisms. 
3-13

Priority: High

b. Methods for detecting and enumerating viruses in source and finished drinking waters

Molecular biology techniques have allowed for the detection of viruses in water samples

but they cannot indicate whether a virus is or is not infectious. To determine infectivity, the virus

needs to be grown in tissue culture. Accurate exposure assessments will not be possible until

these research needs are met.

Improving methods for detection and infectivity assessment of Norwalk virus (EX.M.9)

was considered a high priority because it may be used as a target virus for treatment and/or risk

assessment, especially for ground water systems (see Chapter II, section on ground water

disinfection rule). Methods for virus identification which do not indicate infectivity are generally

of medium priority (EX.M.8). Project EX.M.10 is a high priority because this data will help

determine if viruses other than HAV or Norwalk may be more appropriate for defining

disinfection conditions necessary to protect from viruses in ground and surface water supplies. 

EX.M.8 - Application of PCR technologies and gene probes for virus detection in

water (Ongoing) Conduct studies to evaluate the application of the polymerase chain

reaction and gene probes for virus detection in water. The viruses being studied are

enteric adenovirus, coxsackie virus, hepatitis A viruses, and rotavirus.

Priority: Medium

EX.M.9 - Norwalk virus Develop a cultural method for Norwalk and Norwalk-like

viruses. The objective of this study will be to identify cell culture lines that will replicate

Norwalk virus RNA. Develop PCR/gene probe methods for the in situ detection of the

replicated particles. 

Priority: High

EX.M.10 - Methods for emerging viruses Develop methods for identification and

quantification of emerging viruses.

Priority: High

2. What are the frequencies of occurrence and densities of pathogens in source water,
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finished water, and distribution system water, and what is the population distribution of

exposures to pathogens? What are the sources of pathogens in source waters and finished

drinking water? For example, livestock, wildlife, wastewater management, distribution

systems, etc.

State of the Science

The occurrence and densities of waterborne pathogens in source waters, finished drinking

water, and distribution systems are not well known. Giardia cysts and Cryptosporidium oocysts

have been detected in source waters and also in drinking water samples. In one study, fewer than

20% of the drinking water samples contained Cryptosporidium oocysts, whereas more than 50%

of the surface and spring water samples contained Cryptosporidium oocysts. Giardia cysts were

not found in drinking water samples, but they were detected in surface water samples, including

pristine river water samples. In another study, 78% of watersheds were positive for Giardia on

multiple occasions, while 86% of the sites were multiply-positive for Cryptosporidium. All of

these studies of the occurrence of protozoa in source and drinking waters have limitations. 

Surveys of protozoan cysts and oocysts are few in number and, therefore, difficult to translate to

the national level. The results of the protozoan surveys, although accomplished with state-of-theart methodology, still leave much uncertainty because the method used lacks sensitivity and the

detection of cysts and oocysts does not indicate their viability or whether or not they are

infectious. 

Another major issue is the extent to which watershed control can limit pathogen

concentrations in source waters. While several surveys have indicated lower Giardia and

Cryptosporidium levels in source waters of systems with protected watersheds, the effectiveness

of watershed management practices on reducing pathogen levels is not well defined. However, it

is clear that various sources of watershed contamination will play a significant role in risk

management decisions. EPA recently awarded a grant that will focus on detecting fecal

contamination and its sources in water and watersheds. AWWARF is also sponsoring two

projects in this area; one project is examining the survival of Cryptosporidium and Giardia

exposed to different environmental conditions including water temperature, cyst/oocyst stage, 

and physical stress on the viability and susceptibility to disinfection. Another study will evaluate
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the effects of watershed management practices on pathogen levels in source waters.

There is also insufficient information about viruses in surface and ground waters. Recent

studies indicated that 20% to 25% of all groundwaters were contaminated by enteric viruses

detected by cultural methods and gene probe methods. Gene probe methods detect important

viruses such as hepatitis A virus, rotavirus and Norwalk virus, but they cannot determine if the

viruses are infectious and, therefore, whether they pose a definite risk to exposed individuals. 

This again points to the need to develop tissue culture methods for the more important viruses so

that this significant information gap can be filled. 

 Although we have a relatively good understanding of the linkages between pathogens in

drinking water and illness in water consumers, there are still many questions to be answered, such

as where do pathogens occur, how many are there and where did they come from. Some of the

questions have been answered for selected pathogens. Some studies have been conducted to

determine the occurrence in nature of Giardia and Cryptosporidium , but they have been limited

in scope. National surveys have not been conducted and these are critically needed if the extent

of the potential risk from these organisms is to be defined. Such studies are in the planning

stages. Under the Information Collection Rule, EPA intends to require that source waters and

finished waters at water utilities all over the United States be surveyed to determine the

occurrence of Giardia, Cryptosporidium, enteric viruses, and indicators. This information is

sorely needed for developing the Enhanced Surface Water Treatment Rule. However, since the

ICR will not include intensive monitoring during storm events, optimal regulatory monitoring

strategies to define treatment needs under maximum stress situations will not be apparent unless

additional survey work is conducted. Also, as discussed above, the lack of effective methods for

enumerating pathogens and for indicating whether pathogens are viable or infectious will

compromise the risk assessment process.

Research should be considered for pathogens, especially emerging pathogens, where there

is evidence that they have the potential to become a significant waterborne problem. The

pathogenic protozoa Cyclospora and microsporidia fall into this category. These microorganisms

are transmitted by the fecal-oral route and cause severe gastrointestinal illness; there is some

evidence that they may be waterborne. Anticipatory research should be initiated to determine

how frequently they occur and at what levels in source waters and drinking water. In the event
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that they become a significant problem, exposure assessment information will be available to risk

assessors and managers. Research should also be conducted to determine the extent and densities

of emerging bacterial pathogens, such as Mycobacteria and aeromonads, in drinking water. These

microorganisms are known to be transmitted via the waterborne route and studies have shown the

linkage between water and illness in water consumers. Since the presence of the organisms is not

identified by common measures of drinking water quality, there is no information available on

their occurrence and levels.

Just as the virulence, survival and infectious dose characteristics in microbial pathogens

can vary and affect their ability to cause waterborne disease, there are many characteristics of

exposed individuals and human populations that vary and influence the course of infection and

disease. Areas of uncertainty include: the proportion of the exposed population at highest risk

(such as the immunocompromised, the aged, and very young); how much water is consumed

(boiled vs. non-boiled water, tap vs. bottled water); the extent and effect of protective immunity;

and the significance of other exposures, e.g., foods that carry the same microbial pathogens as

those found in water. Characterizing the nature of exposed populations and their behavioral

patterns will provide valuable information for the risk assessment process.

Research Topics and Priorities

a. Surveys to determine pathogen occurrence in source and finished waters

Research in this area will help in determining optimum survey strategies, sampling frequencies,

and statistical parameters for adequately representing or determining pathogen occurrence in

source waters. Watershed characteristics (e.g., land/water use, population densities, and

hydrology) and temporal storm events are important variables that need to be considered together

when collecting, analyzing and interpreting microbial survey data. In addition, the research will

provide information on whether indicators can be used for estimating source water pathogen

occurrence (ground or surface) or the absence of pathogens in finished waters (ground or

surface). Finally, pathogen occurrence data can be used to evaluate predictions of aquifer

vulnerability.

Project EX.M.11 is considered a high priority because it will supplement ICR information
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by providing data on short-term variations in the microbiological quality of raw and treated water

due to storm runoff and pollution events. Such events and the problems associated with treating

rapidly deteriorating water quality are considered critical risk factors in the occurrence of

waterborne disease outbreaks and spikes in endemic illness (not detected as an outbreak). Data

from this project will clarify the range of pathogen occurrence, potential indicators, and

appropriate targets for defining minimum treatment under the ESWTR, e.g., whether risk

reduction levels could be set based on the 90th percentile level of oocysts detected based on some

minimum frequency of monitoring, e.g., monthly sampling for 18 months. Where year-round

target treatment levels are set, i.e., based on source water measurements and with a monitoring

scheme which is intended to prevent big spikes in endemic levels, has enormous cost/benefit

implications. This study would also validate treatment effectiveness at full-scale treatment plants

by targeting water systems with high source water pathogen loadings. Project EX.M.12 is a

medium priority unless new evidence indicates that emerging viruses are more resistant to

disinfection than HAV or Norwalk.

EX.M.11 - Intensive evaluation of microbiological constituents and treatability in

surface source waters Develop data on short-term fluctuations in pathogen occurrence

related to meteorological and pollution events. These data are needed to evaluate the

effectiveness of treatment and control measures. Validate alternative and prototype

methods for indicators and pathogens. Include microbiological parameters and methods

as in the ICR, but possibly use more effective analytical techniques, should they become

available.

Priority: High 

EX.M.12 - Identification of viruses resistant to disinfection As new virus methods

become available, evaluate new viruses for their potential occurrence in drinking waters

and their resistance to disinfection. Studies should examine which viruses are most likely

to occur in fecally contaminated source waters receiving different levels of disinfection. 

Priority: Medium 

b. Importance of watershed control (including point source, non-point source, and septic

tank controls) for source water pathogen occurrence

Often it is difficult to determine the origin of non-point-source fecal contamination in
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surface water source and therefore difficult to prioritize watershed control measures. Project

EX.M.13 will provide an additional tool for water utilities to assess whether non-point-source

fecal contamination is of animal or human origin. 

EX.M.13 - Distinguish animal versus human sources Distinguish animal from human

sources of pollution using gene probe methodology based on phylogenetic differences

between human and non-human E. coli or Bacteroides or immunoassays for human related

chemicals such as caffeine. These probes will be used to identify sources of pollution. 

Priority: High

 c. Occurrence of and exposure to primary and opportunistic pathogens in distribution

systems

Project EX.M.14 is a high priority because Mycobacterium is relatively more resistant to

disinfection than most other bacteria, and because a published study showed an association

between hospital-acquired infections and this organism in drinking water. Projects EX.M.15 and

EX.M.17 were assigned as high priority because they are expected to provide information which,

in conjunction with the results of other ongoing studies, will establish whether heterotrophic

bacteria in the distribution system pose a risk to immunocompetent individuals. Project EX.M.21

is also a high priority, as it is anticipatory in nature and will address potential pathogens that could

affect both immunocompetent and immunocompromised individuals. Depending on the outcome

of this research (i.e., finding of opportunistic pathogens in the distribution system) the medium or

low priority of the other projects on opportunistic bacteria in this section and in the distribution

system risk management section would be reassessed. 

EX.M.14 - Occurrence of Mycobacterium Determine the occurrence of

Mycobacterium avium (MAC) in potable water distribution systems and compare MAC

water isolates to MAC strains isolated from clinical specimens obtained from

immunocompromised patients. 

Priority: High 

EX.M.15 - Occurrence of heterotrophic bacteria with virulence characteristics 

Determine the frequency of occurrence of heterotrophic bacteria isolated from drinking
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water that demonstrate virulence characteristics.

Priority: High

EX.M.16 - PCR method for Legionella Develop a method for detecting Legionella in

water using the polymerase chain reaction (PCR) procedure. Also determine whether

Legionella growing inside amoebae in potable water can be detected by PCR. 

Priority: Low

EX.M.17- Pathogenicity of heterotrophic bacteria found in drinking water

Conduct surveys to identify heterotrophic opportunistic bacteria associated with drinking

water and granular activated charcoal (GAC) filter effluents. Identify potential pathogens

using compromised animals. Establish a data base for distribution systems on a regional

and national scale. 

Priority: High

EX.M.18 - Occurrence of opportunistic pathogens in biofilms Examine the

occurrence of specific opportunistic pathogens in biofilms associated with treated drinking

water distribution systems and how they are affected by various factors. Organisms of

special concern are Aeromonas, Pseudomonas, and non-tuberculosis Mycobacteria.

Priority: Medium

EX.M.19 - Opportunistic pathogens associated with point-of-use (POU) and pointof-entry (POE) filter effluents Determine the potential for colonization and growth of

opportunistic pathogens in POU/POE water treatment devices and microbial purifiers

under actual use conditions.

Priority: Medium 

EX.M.20 - Potential pathogenicity of heterotrophic bacteria eluted from point-ofuse GAC filters Initial finding indicate that some opportunistic pathogens can grow on

GAC filters. Research is needed to determine the potential for heterotrophic bacteria from

GAC POU filters to cause illness in compromised animal models. Data would be used in

developing human risk estimates.

Priority: Medium
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EX.M.21 - Occurrence of newly emerging pathogens Conduct a national survey to

determine the occurrence of newly emerging and potential pathogens in potable water

distribution systems. Pathogens and opportunistic pathogens of special interest are

Aeromonas, Pseudomonas and Helicobacter. 

Priority: High

EX.M.22 - Exposure as a function of population distribution Conduct a series of

studies to identify exposure as a function of age, other individual susceptibility factors

such as protective immunity, behavioral patterns and environmental factors that affect

water consumption.

Priority: High

3. What are the factors affecting microbial contamination of ground water?

State of the Science

Ground water is the source of drinking water for about 1/3 of the U.S. population. There

are approximately 180,000 community and non-community public water systems utilizing ground

water . About half of the groundwater community systems disinfect, but a majority of the noncommunity systems do not. The drinking water quality of systems that do not treat for pathogens

is dependent on having source waters at the wellhead that do not contain pathogens in sufficient

numbers to cause health problems, and on monitoring for indicator organisms to warn of any

microbial contamination. 

The actual occurrence of pathogens in drinking water originating from ground water is

uncertain. Preliminary results of the ground water survey being carried out by AWWARF

indicate that greater than 20% of the well waters sampled contain viruses. These results are

surprisingly similar to the percentage of systems in which viruses were detected in an earlier

survey of vulnerable ground water systems by EPA and AWWARF. Many state laboratories

report that greater than 40% of the private well waters tested contain coliform bacteria. Records

of waterborne disease outbreaks show that the primary cause of waterborne disease outbreaks

have included ground water that had not been disinfected. This is particularly significant since it is

estimated that these records may underestimate the actual number of outbreaks by an order of
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magnitude.

Although the disease agent in most ground water related outbreaks was unknown, the

majority of outbreaks were believed to be caused by viruses. The primary viruses known to be

agents of waterborne disease are enteric viruses such as polio, coxsackie, echo, hepatitis A and E,

rotavirus, Norwalk, and Norwalk-like. The bacteria primarily responsible for waterborne

outbreaks are Salmonella, Shigella, enteropathogenic Escherichia coli, and Vibrio cholera. The

protozoa, Giardia and Cryptosporidium, are also potential ground water contaminants although

their presence would likely be due to poor well location or construction.

The sources of pathogens in ground water include surface waters, septic tanks, cesspools,

leaking sewer lines, municipal land treatment systems, animal feeding operations, sludge disposal

areas and municipal landfills. Since pathogens must be transported by percolating water from

these sources through the unsaturated zones and then by regional or gradient flow through the 

saturated zones to a well or spring, most control measures are based on placing sources far

enough away from springs or wells that any pathogens will either be physically removed, die or

be inactivated before they reach a place of withdrawal. The extent of removal and die off is

dependent on numerous factors (not all of which have been identified) pertaining to the

characteristics of the pathogens, the nature of the soils and aquifer materials and the distance and

time required for the pathogens to be transported from a source to a well. As a general rule,

viruses are presumed be transported further in the subsurface than either bacteria or protozoa due

to their much smaller size.

Methods in use or proposed for determining whether a well or spring is in danger from a

potential source of contamination range from using arbitrary setback distances to some type of 

vulnerability assessment method to predict the relative vulnerability of a water well or spring to

contamination by pathogens. A variety of methods have been proposed for doing ground water

vulnerability assessments including a) methods that give numerical ratings to the physical factors

(such as soil types, geology, and depth to ground water) that affect ground water vulnerability to

contamination by pathogens, and b) mathematical models. Additionally, decision trees that

combine several methods in an ordered manner may be the most effective way to make this

determination. 
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Arbitrary setback distances are very difficult to defend scientifically, but are the easiest to

implement from a regulatory standpoint. The use of vulnerability indexes or avoidance criteria to

assess the vulnerability of groundwater to pathogens has great potential for screening purposes,

but the use of vulnerability assessment methods in general has been questioned by the scientific

community if such methods are going to be used for making site-specific decisions. The use of

such methods will probably require extensive evaluation and testing before they are accepted as

regulatory tools. Efforts are being initiated by EPA to develop avoidance criteria for the Ground

Water Disinfection Rule (GWDR). 

The use of predictive computer models for making regulatory decisions regarding

disinfection of ground water has had difficulty in gaining regulatory acceptance although

significant advances have been made in the development of mathematical models to predict the

transport and survival of pathogens in the subsurface. A key element of these models is the

inactivation rate chosen for the pathogens (viruses). Survival times for many of the primary

pathogens of concern in the subsurface and in ground water are unknown. Existing information

about a few pathogens suggests that the die off of bacterial pathogens is much faster than viruses,

and that survival times longer than one year for viruses would be unlikely. However, data on

inactivation rates for pathogens under the various subsurface conditions are limited and

contradictory. A critical need is to better determine these inactivation rates in the unsaturated

and saturated soils and aquifers. Limited additional work in this area has recently been funded by

AWWARF, but a more extensive effort is needed.

The major hindrance in obtaining final acceptance for any vulnerability assessment tool is

the extensive field testing needed to confirm the tool’s protective capability for making sitespecific decisions. Extensive field validation is extremely difficult, time-consuming and expensive

and the number of field tests that can be performed is limited by a lack of available resources.

The majority of ground water-based public water supplies (at least 140,000) are very

small, non-community systems with extremely limited resources. For these systems, virus fate and

transport models will not be appropriate for predicting vulnerability. Vulnerability assessments

might best be made through a sanitary survey and wellhead protection approaches. Therefore,

general hydrogeological and land use criteria must be considered and tested for their utility in
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predicting vulnerability. A high priority exists for developing practical cost-effective approaches. 

The approach eventually chosen is likely to be a decision tree that combines elements of several

methods in a structured prioritized manner.

 On July 10 - 11, 1996, the EPA’s Office of Ground Water and Drinking Water conducted a

Workshop on Predicting Microbial Contamination of Groundwater Systems. Workshop

participants identified the following indicators as potentially useful for predicting fecal

contamination of ground water: E. Coli, Enterococci, Clostridium perfringens, and Coliphages

(somatic and male-specific). The following research on indicators of fecal contamination of

ground water was identified at the workshop: Determining how the survival and occurrence of

Clostridium perfringens correlates with the occurrence of pathogens in contaminated ground

waters; delineating the range of hosts for somatic coliphages to determine whether they have

enough specificity as an indicator of fecal contamination; and measuring the occurrence of malespecific coliphages in small populations to determine whether they have enough sensitivity to use

for small systems (< 100 people). Where appropriate to do so, the projects described below

incorporate the recommendations of the workshop. 

Research Topics and Priorities

a. Survival and transport of pathogens in the subsurface

Determination of the survival times of pathogens, especially viruses, in both the saturated

and unsaturated subsurface is the major research need for any method for determining whether

ground water does or does not have to be disinfected. Information on virus inactivation times in

the subsurface for many major viral pathogens is nearly nonexistent. Survival data must be in a

form that can be incorporated into decision-support systems for determining whether ground

water should not be disinfected. Information on the factors determining the extent of transport of

pathogens in different hydrogeologic settings, especially where preferential flow paths exist and in

the unsaturated zone, is also a major need if transport models are going to be used.

Project EX.M.23 is considered high priority because it addresses an area of high risk: the

concentration and occurrence of a major group of contaminants – viruses. It also is an area in

which currently there is a high degree of uncertainty. For similar reasons, project EX.M.24 is also

a high priority. The assessment of viral behavior in the subsurface requires knowledge of both
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their fate and transport, which are intimately linked. Furthermore, once viral die-off rates are

determined, the data can be applied to many models for estimating set-back distances. Project

EX.M.26 is considered high priority because this approach has the most promise for developing

practical criteria that can be implemented, even if such criteria may apply only to a limited number

of hydrogeological situations. Currently, there is a high degree of uncertainty in assessing the

vulnerability of ground water to contaminants. Projects EX.M.29 and EX.M.33 are considered

high priority because participants from the Workshop on Predicting Microbial Contamination of

Groundwater Systems considered this research as critical for supporting the Ground Water

Disinfection Rule. The other projects are considered medium priority because the feasibility of

success in generating criteria that can be practically implemented is very uncertain, and research in

this area is already underway.

EX.M.23 - Virus survival in the subsurface Inactivation times for the viral pathogens

of regulatory concern are not known for most soil types and conditions. This work would

determine inactivation times of viral pathogens in several ground waters and soils under

both unsaturated and saturated conditions. The project will focus on the role of

subsurface ecology, including both geochemical and biological factors such as predation,

as a determinant of subsurface virus survival. Initial work will use bacteriophages as

surrogates for human enteric viruses. Controlled laboratory experiments with human

enteric viruses will be used to confirm that the mechanisms that control bacteriophage

survival also control enteric virus survival. 

Priority: High 

EX.M.24 - Virus transport in the subsurface Methods are needed for predicting the

transport time between wells and springs and sources of pathogens. This research would

evaluate the factors which govern the transport of viral pathogens in both the unsaturated

and saturated zones of the subsurface. Subsequently, methods would be developed for 

incorporating this information into either predictive models or decision-support systems

for determining whether ground water should not be disinfected. 

Priority: High
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b. Methods for protecting wells and springs from pathogens

Scientifically defensible methods for determining setbacks between sources and wells or

springs are needed to aid decision makers in determining whether ground water achieves “natural

disinfection” or if chemical disinfection is required. Additional evaluation/testing of proposed

mathematical models such as CANVAS is needed to address scientific or regulatory concerns. 

Methods to assess the vulnerability of ground water to pathogens by the development of

vulnerability indexes should be critically evaluated and tested. Both vulnerability rating

systems/models may require additional field tests. 

EX.M.25 -Viral transport and fate models Critical evaluation of the use of

mathematical viral fate and transport models for making decisions on whether drinking

water from ground water sources should or should not be disinfected. Emphasis will be

placed on the feasibility and reliability of existing models. Available information and data

will be used when possible.

Priority: Medium 

EX.M.26 - Vulnerability of ground-water to pathogens Critical evaluation,

emphasizing feasibility and reliability, of methods being developed to assess the

vulnerability of ground water to pathogens by the development of vulnerability assessment

systems. Available information and data will be used when possible. 

Priority: High

EX.M.27 - Delineation of natural protection zones Examine and test an alternative

method to conventional contaminant transport models and vulnerability assessment

methods for delineating a protective zone around a well or spring. The method will

integrate the analytical element method for delineation of time-of-travel capture zones

with information on survival and transport of pathogens. The capture zone concept will

be tested with data developed under the New England virus study.

Priority: Medium

EX.M.28 - Ground water vulnerability and sensitivity assessment methods This

research examines the range of physical, biological, institutional and operational factors

that could be used to determine these vulnerabilities, including (but not limited to)
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hydrogeological factors, land uses and ground water/wellhead protection program

determinations. The ultimate product is to be a pragmatic, field-tested assessment

methodology that, given generally available information, can estimate vulnerability to

microbial contamination in small-to-medium ground water systems. It may result in

separate approaches for larger and smaller systems, based on economic feasibility. Initial

work has been to develop appropriate criteria. Subsequent work will be to field validate

the criteria against carefully described vulnerable and non-vulnerable systems. 

Priority: High

EX.M.29 - Occurrence of Clostridium perfringens in the subsurface C. perfringens

will be collected from over 100 groundwater sites as part of a larger virus survey.

Priority: High

EX.M.30a - National aquifer and well map A random selection of drinking water

systems using ground water was mapped onto USGS aquifer maps on a state-by-state

basis. Community, non-community and transient systems were mapped separately based

on their zip codes.(Completed 1995)

Priority: Medium

EX.M.30b -Sensitivity mapping A random selection of drinking water systems using

ground water was mapped onto USGS aquifer maps on a state-by-state basis. 

Community, non-community and transient systems were mapped separately based on their

zip codes. (Completed 1995)

Priority: Medium 

EX.M.31 - Correlation of water age and microbial viability This work would

investigate the relationship between water age and the presence of human enteric viruses. 

Priority: High 

EX.M.32 - New York City Watershed Protection Septic Siting Study. The septic

system types to be investigated include continuous use functioning systems, weekend use

systems, seasonal use systems and newly installed systems, both residential and
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commercial. Study sites will be representative of varying hydrological, chemical, physical

and design parameters. A minimum of three sites will be selected for the Phase 1

investigation, which includes site selection, installation of five monitoring wells at each site

and baseline data collection. Phase II will include spiking studies using phage, bacterial or

other tracers.

Priority: High

EX.M.33 - Phase 2 Virus Sampling and Phage Research for the Santa Ana River

Water Quality and Health Study (includes Virus Testing of Ground water for

GWDR and Santa Ana River Water Quality and Health Study) Samples of ground

water and river water will be taken monthly for virus cell culture and PCR analysis.

Bacteriophage and coliform samples will also be taken. Phage will be evaluated as

indicator organisms for enteric viruses. All production and monitoring wells sampled in

the first project year were negative for enteric viruses.

Priority: High

D. RISK ASSESSMENT

1. How can the risks posed by pathogens in drinking water be characterized?

State of Science

The Agency has not established a formal methodology to assess the risk for microbial

contaminants as it has for chemicals. In 1991, a joint EPA/AWWARF conference evaluating

drinking water and health in the year 2000 proposed the application of the National Academy of

Science risk paradigm for microbial contaminants. However, as discussed previously microbial

risk assessment is relatively new and the issues that need to be addressed are more complex than

those currently used for defining chemical risks. The 1996 Safe Drinking Water Act Amendments

(SDWAA) contains provisions that focus on the need to ensure that adequate health protection is

conferred to the most sensitive subpopulations, especially children, in all future drinking water

regulations, taking into consideration, cost and benefit of disease prevention or control. Pathogen

interactions may pose overwhelming health risks to some groups of individuals such as infants,

young children, the malnourished, the elderly or immuno-compromised individuals. Under the FY
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97 SDWAA initiative additional resources have been identified for the expansion of research

efforts relating to pathogen risk assessment. The focus of risk assessment studies has been on

infectivity and determinations of the smallest pathogenic dose (numbers of infectious

microorganisms) able to produce an infection in healthy individuals. Studies are needed in

selected subpopulations to determine host susceptibilities (lack of or reduced capacity of host

resistance and defense mechanisms) and relationship to pathogen entry and establishment of

infection or other forms of parasitism (e.g., transient carrier state, colonization, pathogenic

interaction). Studies are needed to relate pathogen virulence and host resistance so that risk

assessments can be made about carrier states, colonization, infection, disease course and outcome

(e.g., clinically asymptomatic persons, disease state, full recovery, chronic debilitate recovery,

mortality). Increased efforts will include research to assess and quantify effects of immunity of

exposed individual and population; evaluation and quantification of the disease process including

secondary spread, magnitude and severity of effects, in addition to infection and the effects of

multiple exposures and routes of exposure. 

Previously, a risk assessment model was developed for Giardia contamination in drinking

water by Rose, et al., 1991, in which dose-response data from human volunteer studies were

modeled using a Poisson distribution. Actual dose-response curves were developed using a lowdose extrapolation model and a maximum likelihood estimate. Based on various input variables,

such as number of organisms and mean response rate, the risk of infection and the risks of disease

were estimated, including risk from exposure to a single organism. Log order reductions of cysts

from source water needed to achieve an acceptable risk level (e.g., less than one infection per

10,000 people per year) can be calculated using this approach. However, as noted before, there

are many variables that need to be taken into account for pathogen risk assessment that are not

currently being addressed in this approach, such as age, severity of response, or host immunity. 

Although, similar models have been typically used in the quantitation of chemical carcinogens,

risks associated with pathogenic exposures may be biologically more compatible with other

approaches for evaluating dose-response relationships for pathogens. Therefore, model validation

research will be expanded to include a comprehensive evaluation of several statistical models. Of

particular concern are the risks posed to children and other potentially susceptible populations. 

Research efforts have been expanded to address issues relating to quantitatively and qualitatively

measuring and characterizing risks to these populations. These approaches will allow for the

development of risk estimates following acute or chronic exposures and address issues such as
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sensitivity, multiple endpoints and severity. The evaluation of these additional approaches for

pathogenic assessment are needed, therefore, to augment current dose-response models for

quantifying risks. 

Research Topics and Priorities

a. Modification of risk assessment paradigm for characterizing microbial risks

RA.M.1 - Development of a comprehensive microbiology risk assessment model for

water (Ongoing) This project is a high priority because EPA needs a suitable and

comprehensive microbiological risk assessment model for water (drinking, recreational,

shellfish, wastewater, reuse) in order to establish or modify drinking water and water

quality standards for pathogens or their indicators. This project will identify the proper

elements and processes needed to perform microbial risk assessment. Existing paradigms

such as the National Academy of Sciences chemical risk assessment approach and the

ecological risk assessment approach will be used as the starting point and these will be

modified and amended for microbial risk assessment. The selected approach will be

validated with case studies. 

Priority: High

b. Accuracy of dose-response models in predicting waterborne disease

The goal of this effort will be to develop both qualitative and quantitative microbiological

exposure response models, validate/ confirm input assumptions and characterize the uncertainties

surrounding those assumptions. Unlike previous studies, dose-response data will be analyzed and

evaluated using various statistical approaches such as using a logistic regression model similar to

that developed to characterize the risks from non-cancer effects. These projects are high priority

because models will address issues relating to the magnitude of response and accounts for severity

of effects and duration of exposures. These studies will enhance current efforts and allow for

better comparisons of effects other than infection, such as respiratory disease, diabetes and

immune deficiency. Of particular concern are the risks posed to children and other potentially

susceptible populations. Research efforts have been expanded to address issues relating to

quantitatively and qualitatively measuring and characterizing risks to these populations.

RA.M.2 - Evaluation/Application of various dose-response relationship models for
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quantitating pathogenic risks 

2a Evaluation of various dose-response relationship models

Conduct extensive literature search to evaluate all available data relating to adverse effects

and dose-response for Giardia and Cryptosporidium and other pathogens of concern. 

Research will then be conducted in two phases. Initial efforts focus on the development

and evaluation of statistical approaches used to characterize the dose-response relationship

for humans exposed to waterborne pathogens. Phase 2 will include the analysis of doseresponse data from existing studies comparing the various statistical approaches including

logistic regression. Model application and severity of effects categorization will be tested

using data for bacteria, protozoans and viruses. As appropriate, quantitative estimates will

be developed for establishing risk levels for specific pathogens. This research will provide

relevant information on the virulence of risks associated with a specific pathogen and

individuals or populations at risk, as well as supporting development of regulatory

guidelines/ criteria.

Priority: High

2b Virulence Factors and Host Susceptibility: Impact of waterborne pathogens on

human subpopulations

Under the FY 97 SDWAA initiative, additional resources have been identified for the

expansion of research efforts relating to pathogen risk assessment. Increased efforts will

include research to assess and quantify effects of immunity of the exposed individual and

population; evaluation and quantification of the disease process including secondary

spread, magnitude and severity of effects in addition to infection and the effects, of

multiple exposures and routes of exposures.

 

c. Characterization of risks posed by exposure to multiple or complex mixtures of

pathogens

Similar to chemical exposures in drinking water, microbial exposures occur in conjunction

with chemical or other pathogenic exposures by multiple routes. While much has been done in the

development of models for estimating risks for chemical mixtures, very little information is

available regarding the risks associated with mixed or multiple pathogenic exposures. The overall

impact of microbial-environmental interactions, microbial-chemical interactions, and microbialmicrobial interactions to changes in emergent populations on water quality has not been
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thoroughly evaluated. Source waters containing acids, organochemicals, or heavy metals can

damage or kill biological waste treatment microbial colonies and again may enhance growth of

disinfectant resistant pathogens. Such microorganisms may be able to metabolize water

disinfectants to reduce their effectiveness. Microorganisms also can metabolize other chemical

contaminants to potentially toxic compounds, as well as produce toxic compounds effective in

pathogenic interactions (enterotoxins, lysins, and hemolysins to enhance invasiveness and tissue

destruction). Assessment risks of waterborne toxins from algal blooms or bacterial overgrowth

can be predicted based on knowledge of the organisms present in ground or surface waters and in

the distribution system, survival and growth enhancing mechanisms of nutrient abundance, and

waste run-off. The potential for co-infection between enteric viruses and bacteria to enhance

adverse health effects will be explored. For most pathogenic agents, exposure is expected to be

extremely low or zero within the system. The greatest potential for mixed or multiple

contaminant exposure occurs with bacteria due to their capability for regrowth and biofilm

development within the distribution system. Interactions between microorganisms during mixed

infections have yet to be investigated, (e.g., interactions, such as the reported ability of

Coxsackievirus to increase host susceptibility to Shigella). Chemical, environmental, and

microbial interactions could contribute to low-level human and animal population exposures, e.g.,

liver tumor, promoter toxins (microcystin-LR). Microcystin-LR produced by cyanobacteria

during water blooms may contribute to liver tumor promotion in the exposed populations. 

Endemic disease of unknown etiology could be the result of human exposure to low levels of

waterborne microbial toxins. Research is needed to address the impacts of multiple exposures of

pathogens or mixed exposures (i.e., chemical and microbial exposure) on immune response and

effects levels. Development of a preliminary assessment of the existing available information and

framing of the scope and magnitude of this issue is also needed.

RA.M.3 - Evaluation and application of issues and methods to assess risk associated

with exposures to multiple pathogens, routes, disease course and outcomes and

duration

3a Feasibility Assessment on Interactions Conduct a preliminary assessment and frame

issues related to mixed exposures of pathogens in drinking water. This preliminary

assessment would include an evaluation of existing data relating to mixtures and potential
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interactions, and identify issues needed to be address and research needs. Future research

projects will be developed and prioritized based on the research issues and needs identified

in the preliminary assessment of mixtures.

Priority: Medium

3b Research would also be conducted to test the application of dose-response

models/approaches for identifying and estimating risks for multiple pathogens. The

emphasis of this effort will be to address bacterial agents where the greatest potential for

mixed exposures may occur. A dose-response plane would be developed using individual

dose-response curves from various pathogens or chemicals and pathogens. Validation

studies would be conducted using an appropriate animal for pathogenic response and

multiple exposures scenarios. Study design would include sequential chemical and

pathogenic exposures as well as continuous exposures at subthreshold doses. This

research is low priority because of the lack of general methods for assessing mixtures and

the need to develop single pathogen health and exposure data.

Priority: Low

E. RISK MANAGEMENT RESEARCH

Disinfectants are used by virtually all surface water systems in the U.S. and by an

unknown percentage of systems that rely on ground water. Chlorine has been the most widely

used and most cost-effective disinfectant. Disinfection is most efficient when it is applied as part

of the multiple barrier concept; that is, use of the best available water source, protection of that

source from contamination, and use of water treatment to remove and inactivate pathogens. 

Recently there has been growing recognition that water quality can deteriorate dramatically during

distribution. Therefore, another part of the barrier to infectious disease is a properly designed and

operated distribution system. Each component of our research is designed to evaluate the

effectiveness of one of more of these barriers and will collectively provide information on the

combined effectiveness of these barriers.

While disinfection is an integral part of water treatment, filtration may be necessary to

reduce pathogen levels and make disinfection more reliable by removing turbidity and other

interfering constituents. For example, in the United States the waterborne disease outbreak rate
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for communities using surface sources without filtration is eight-fold greater than communities

with filtered water systems. Properly designed and operated water treatment systems that include

filtration and disinfection can greatly reduce the risk of waterborne disease. There is a need,

however, to find the proper balance between controlling risks from microbial pathogens and

disinfection by-products. 

This section deals primarily with the treatment and distribution system research needed to

support regulation development for control of microbial pathogens. This research must be

conducted as an integrated program with the research described for controlling disinfection byproducts (see Chapter IV). Separate studies not discussed in this section but which are

complementary to this research deal with development of cost/benefit methodology, which can be

utilized to make effective risk management decisions. 

1. How effective are various treatment processes in removing/inactivating pathogens?

State of the Science

The primary processes for removing pathogens from drinking water are water treatment

filtration systems and disinfection. For filtration systems the specific sequence and type of unit

processes to be used are dependent on source water quality. Optimized treatment trains will lead

to a low probability of pathogens entering the distribution system. Breakdowns, such as in

equipment or lapses in operational control, can lead to significant problems.

The disinfection process is the final treatment barrier for minimizing pathogen

transmission. In some cases, disinfection may be the only treatment barrier (e.g., a disinfected

ground water supply). In either case, the disinfection process must also be optimized to aid in

removing pathogens. Water plants must remove as much particulate material (e.g., clays,

microbes, etc) as possible in order to increase the effectiveness of disinfection.

EPA and others have been conducting research on pathogen removal and inactivation of

microorganisms for many years, although the types of pathogens studied and associated removal

processes evaluated have varied over this period. However, improvements in treatment
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technology, pathogen detection and an increased understanding of waterborne disease etiology

have increased the need for research in this area. More sophisticated monitoring requirements

have led to rethinking of which treatment processes should be used and how these processes

should be operated. Most current research on pathogen removal has focused and will continue to

focus on Cryptosporidium oocyst removal and inactivation because it is an excellent surrogate for

treatment efficiency. However, new pathogens such as Microsporidia and Cyclospora

cayetanensis are appearing on the horizon and may pose even greater challenges in the future. 

Therefore, as we make progress in answering important questions regarding the treatment of

Cryptosporidium, future efforts will move toward addressing the treatability of other waterborne

pathogens as their existence and significance is recognized. The pathogens of greatest concern in

ground water sources (especially the enteric viruses) are different from those occurring in surface

sources and information on treatment alternatives that are effective against viruses are needed to

identify appropriate treatment where needed.

EPA and the American Water Works Association Research Foundation (AWWARF) are

conducting the majority of the treatment research in the United States. EPA has conducted

filtration studies with both conventional and alternative filtration processes for removal of

pathogens. Information gathered from those studies has led to implementation of the Surface

Water Treatment Rule and has provided guidance to many water utilities. AWWARF is currently

funding research intended to develop design and operational criteria for the optimization of

various treatment processes to remove protozoan cysts, specifically Giardia and Cryptosporidium. 

Parallel studies are being conducted to determine if a relationship exists between cyst removal and

the removal of cyst-sized particles. AWWARF plans to conduct studies at utility-owned pilotand full- sized facilities. Research is being conducted to assess particle-size analysis as a means of

optimizing filtration and the impact of sequential disinfection on the survival of Cryptosporidium

oocysts. This information will be used in workshops and guidance documents to assist drinking

water utilities to more effectively operate drinking water treatment plants. Surveys of water

utility performance and studies in detection methods have been funded by AWWARF and are

currently ongoing. Montgomery Watson is conducting a disinfection study of approximately 20

utilities; the study should define disinfection conditions necessary for Cryptosporidium

inactivation using multiple sequential disinfectants. The American Water Works Association

(AWWA) through its Water Industry Technical Action Fund (WITAF), the Water Research

Center in the UK, and many others are also studying pathogen removal/inactivation processes. 
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AWWARF has recently initiated studies to begin evaluating the effectiveness of conventional and

innovative treatment processes for removing and inactivating selected emerging waterborne

pathogens. 

EPA is conducting research on the use of slow sand filters for removing oocysts, and

conducting comparative jar tests for evaluating removal rates of preserved versus unpreserved

oocysts. Pilot conventional and direct filtration systems are being spiked with fresh oocysts to

determine optimal removal conditions. The removal of particles by conventional and enhanced

filtration is being studied. Total particle counts, particle counts in the oocyst size range and

indigenous bacterial spores are being studied as possible surrogates for oocysts. There is

evidence that oocysts may be damaged through treatment and therefore susceptible to

disinfection. It has also been observed that 3-5 micron-sized oocysts may be able to fold or

squeeze through 3-micron membranes under pressure. In addition, a series of studies is being

conducted that evaluate the effectiveness of biological treatment plus final disinfection on the

removal of oocysts, spores, and DBP precursors. Several small-system technologies such as

diatomaceous earth and membrane package plants are being evaluated. EPA is also conducting

studies on cyst viability and on treatment effectiveness under varying conditions, e.g., storm

events with high turbidity and high pathogen loadings, etc.

There are a number of questions to be answered with regard to the removal/inactivation of

pathogens from drinking water. The Milwaukee experience reinforces the need to find answers to

these questions which include a more complete understanding of the optimization of filtration for

removing pathogens, the role of disinfection, and the types of technology that might be useful for

small utilities.

Results from research to date indicate that there is much to be learned regarding the

conditions that lead to optimal operation of drinking water treatment plants for the removal of

oocysts and other pathogens. For example, it has become apparent that oocysts have physical

properties that make them both difficult to remove and very resistant to disinfection. Research

has shown that the organism is flexible and that it can penetrate porus media. In contrast, it is

also sticky so that it adheres to unit process walls and piping making removal difficult to

calculate. It has a surface charge that is different from particles normally found in water, so that

standard coagulation procedures may not adequately remove oocysts during conventional
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treatment (coagulation, settling, filtration and disinfection). Results from EPA studies have

shown that preserved oocysts which are normally used in treatment research and are most

convenient for spiking studies do not behave in the same way as natural oocysts. Therefore, more

studies on treatment effectiveness need to be conducted using natural oocysts. Because oocysts

are pathogens and cannot be spiked into operational treatment plants, there is need for the

development of surrogates which are nonpathogens but behave in the same manner as oocysts. 

Small systems present a special problem because the technologies used must be easy to operate

and have low maintenance requirements. However, as has been discussed, removal of oocysts

requires careful attention to operational detail. This was one of the major lessons learned from

Milwaukee.

Bench scale, pilot plant and field-scale studies will be required to address these research

issues. Initially, technology evaluations will be conducted at bench- and pilot-scale. This will be

followed by field studies (RM.M.5) of the most promising technologies which will evaluate their

ability to control both pathogens and DBPs. In general, these field studies will be conducted at

sites where these technologies are being utilized by certain utilities such that evaluations of the

important operating parameters can be conducted and results can be compared with full-scale

operations. New techniques for monitoring treatment plant effluents and for process control will

also be investigated. Improved electronic measuring techniques could allow for real-time

measurement of treated water quality. All future projects will incorporate multiple pathogen

removal, surrogate analysis and DBP reduction efforts as part of the research protocol.

Research Topics and Priorities

a. Optimization of conventional treatment processes to remove pathogens

All of the projects listed below except RM.M.28 are considered high priority and were

selected for consideration because they address the major scientific unknowns: removal of oocysts

via conventional treatment, development of surrogates for oocyst removal, and viability of

oocysts through multiple treatment steps. Results of these studies will provide information

necessary for setting feasible risk based treatment levels. They also provide the data to develop

practical performance monitoring procedures using surrogates and to determine whether

compliance is achieved for meeting level of treatment requirements. Projects 2, 3 and 4 expand

on current promising research efforts by EPA. RM.M.28 is considered medium priority at this

time until the existence and significance of specific emerging pathogens is better defined.
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 RM.M.1 - Filtration studies for controlling pathogens (Ongoing) Bench-scale and

pilot scale studies have been conducted to evaluate pathogen removal mechanisms. 

Current studies are attempting to find surrogates for pathogens or surrogates for treatment

evaluation. Particle counting, zeta potential, microbial counting and other techniques are

used to determine removal of pathogens. Criteria for measuring damage to oocysts are

also being developed.

Priority: High

RM.M.2 - Filtration removal of protozoa and indicators Conduct pilot-scale studies

to assess conventional water treatment and direct filtration for removal of protozoans and

indicators.

Priority: High

RM.M.3 - Optimize conventional treatment for removal of oocysts Conduct bench

studies to evaluate and demonstrate that, if treatment (coagulation/ settling) is optimized

for turbidity/spore/particulate reduction, coincidental removal of oocysts occurs. 

Determine if there are some coagulants that are selective for removing oocysts.

Priority: High

RM.M.4 - Filtration damage viability studies Conduct bench and pilot studies to

assess the capacity of oocysts to remain viable through various types of treatment. 

Conduct disinfection studies to determine if oocysts that are damaged by passing through

treatment are more easily inactivated than undamaged oocysts.

Priority: High

RM.M.5 - Evaluate disinfection and optimization in field-scale treatment plants

Conduct field-scale studies of pathogen and DBP control at existing water treatment

plants. Use oocysts, spores, particle and turbidity analysis as part of the evaluation 

process. (This is a component of Project EX.M.11)

Priority: High

RM.M.28 - Evaluation of the effectiveness of conventional treatment processes on
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removing and inactivating emerging pathogens As the existence and significance of

new, emerging pathogens are identified by NERL and NHEERL researchers, NRMRL will

initiate research on the effectiveness of conventional treatment to remove and inactivate

these pathogens.

Priority: Medium

b. Effectiveness of different filtration processes in removing pathogens

The research described in these projects represent variations of conventional treatment. 

Biological treatment is rated “high” because it has the potential for controlling DBPs and

pathogens simultaneously. Task RM.M.7 is rated “medium” because the technologies are

expected to have similar results for Cryptosporidium as for Giardia, on which a number of studies

have already been conducted. RM.M.29 is considered medium priority at this time until the

existence and significance of specific emerging pathogens is better defined.

RM.M.6 - Biological treatment for control of oocysts

Conduct studies on the effectiveness of biological treatment for control of oocysts while

simultaneously controlling disinfection by-products.

Priority: High

 

RM.M.7 - Filtration techniques other than conventional treatment Examine other

filtration techniques such as diatomaceous earth filtration and slow sand filtration to

determine how Cryptosporidium removals compare with those of Giardia (already

determined from previous studies).

Priority: Medium

RM.M.29 - Evaluation of different filtration processes on removing emerging

pathogens As the existence and significance of new, emerging pathogens are identified by

NERL and NHEERL researchers, NRMRL will initiate research on the effectiveness 

of innovative filtration processes to remove these pathogens.

Priority: Medium

(See also project RM.M.14 below)
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c. Effectiveness of disinfection processes in inactivating pathogens

Research is needed on the disinfection effectiveness of various disinfectants for viruses and

protozoa. For example, some research suggests that reductions in viable Cryptosporidium

oocysts are achieved after sequential disinfection using different disinfectants (i.e.

chlorine/chloramine, ozone/chloramine). EPA uses disinfection data on hepatitis A virus (HAV)

for estimating conditions necessary to inactivate viruses because of its relatively high resistance to

disinfection. Norwalk virus, which has also caused waterborne disease outbreaks, may be more

resistant to disinfection than HAV and therefore may be more suitable than HAV for defining

adequacy of disinfection. 

Establishing whether Norwalk virus is more resistant to disinfection than HAV is

particularly important for ground water systems. However, it is also relevant for surface water

systems which use physical means for removal of protozoa and must provide a minimum

disinfectant dose to assure adequate virus removal/ inactivation. Because of its potential to

reduce health risk, project RM.M.8 was assigned a high priority. A Norwalk virus project on UV

inactivation was also assigned a high priority because of its potential usefulness for disinfecting

ground water. (Norwalk virus was not included in the AWWARF UV virus inactivation study.) 

In addition, systems using ground waters will need information on other treatment alternatives

that are effective against viruses, as this is an important consideration of deciding on ground water

disinfection methods. Therefore, RM.M.30 is a high priority project. RM.M.31 is considered

medium priority at this time until the existence and significance of specific emerging pathogens is

better defined.

Project RM.M.10 on sequential disinfection treatment, which will expand on AWWARF's

and Montgomery Watson’s research, was assigned a high priority because it is expected to

develop criteria for more efficient and cost-effective disinfection strategies. This additional

research is needed to develop a generic model concept by which utilities with different operating

conditions could estimate inactivation efficiencies.

RM.M.8 - Control of Norwalk virus by chlorine and ozone

Compare kinetics of Norwalk virus inactivation to that of poliovirus 1 and MS-2

coliphage, and determine the extent of removal by pretreatment and filtration and the
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extent of inactivation with chlorine or ozone.

Priority: High

 RM.M.9 - UV disinfection efficiencies for Norwalk viruses 

Evaluate efficiency of ultraviolet light for inactivation of Norwalk virus, and determine

UV intensity and exposure time to achieve 1,2,3 and 4 log inactivation. 10

Priority: High

 RM.M.10 - Inactivation of Giardia and Cryptosporidium by sequential

disinfectants Define the treatment conditions (concentration, contact time, temperature)

needed to inactivate Giardia and Cryptosporidium with different sequential disinfectants. 

Priority: High 

RM.M.30 - Evaluation of alternative inactivation processes for controlling viruses 

Evaluate other innovative advanced oxidation processes and removal systems such as

ultrafiltration membranes, mixed oxidant generators, TiO and UV and combinations of 2

these processes for removing and inactivating viruses. This project is closely related to

RM.D.7. 

Priority: High 

RM.M.31 - Evaluation of different disinfection processes in inactivating emerging

pathogens As the existence and significance of new, emerging pathogens are identified by

NERL and NHEERL researchers, NRMRL will initiate research on the effectiveness of

innovative disinfection processes to inactivate these pathogens.

Priority: Medium

Other projects that also address this topic:

RM.M.3 - Optimize conventional treatment for removal of oocysts

RM.M.5 - Evaluate disinfection and optimization in full-scale treatment plants

RM.D.2 - Effects of ozone and biofiltration for control of precursors, pathogens and

for pesticide removal

RM.D.7 - Membranes/advanced oxidation & other technology combinations
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d. Appropriateness and costs of technologies for small systems

Any changes in regulations requiring small systems to upgrade treatment for Giardia or

Cryptosporidium would be a major challenge because of their limited financial resources for

acquiring and operating drinking water treatment plants. In addition, most utilities have difficulty

in finding and retaining qualified operators. In setting any new regulatory criteria for small

systems, EPA needs information on the effectiveness, costs and feasibility of appropriate

treatment technologies. Therefore, research projects to develop and demonstrate small-scale,

cost-effective treatment technologies which are easily installed and automated, and which do not

require highly skilled operators are a high priority. Developing cost curves will be an important

element of all small-system technology projects.

RM.M.11 Cryptosporidium removal using bag filters Identify vessel, bag, and basket

design characteristics for optimal removal and treatment train requirements relative to

variable raw water characteristics. Operational factors relative to cost and performance

should also be considered.

Priority: High

 RM.M.12 - Cost-effectiveness of prefiltration for ultrafiltration unit Determine range

of raw water characteristics relative to various pre-treatment technologies used to increase

membrane life, reduce maintenance costs, and enhance DBP precursor removal. This is

cross-referenced with RM.M.17, RM.M.18, and RM.M.20.

Priority: High 

RM.M.13 - Development/testing of innovative technologies for small systems 

Conduct studies on new synthetic resins, pulsed UV, electron beam irradiation, highpressure distillation, non-porous hollow fiber membranes, and cartridge filtration . In

addition, conduct verification testing of package drinking water systems for use by small 

communities. This work should be coordinated with RM.M.4, RM.M.10, RM.M.30 and

RM.D.7.

Priority: High
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2. How can the quality of treated water be maintained in distribution systems?

State of the Science

While much waterborne disease is associated with contaminated water sources and

inadequate water treatment, protection of water quality during distribution to the customer is

often neglected. Continuous, adequate water pressure and residual level of disinfectant are

important, especially in areas lacking adequate sewerage and sewage disposal facilities. Sewage

and contaminated surface or ground water can enter the water system through cross-connections

and broken or leaky water pipes in older and poorly maintained water distribution systems. In the

United States, 24% of the waterborne outbreaks reported in community water systems over the

past decade were caused by contamination entering the water distribution system, i.e., not

originating from poorly treated water. To lower the risks of waterborne disease, contamination of

water distribution systems must also be prevented. 

Maintenance of a disinfectant residual is required to provide an additional barrier of

protection from pathogens that might penetrate the water distribution system; however, the

effectiveness of this residual to protect against significant contamination through a crossconnection or infiltration is uncertain. The real value of maintaining a disinfectant residual in the

distribution system is to help identify the occurrence of such contamination by monitoring for the

loss of the residual. Although the behavior of some constituents in the distribution system,

namely chlorine, has been well studied, the fate of others is less known. These include alternative

disinfectants (such as chloramines), biologically assimilable organic carbon, particulate material

(including microorganisms), and genotoxicity . Better characterization of water quality problems

is needed particularly at dead end branches where stagnant flow conditions prevail.

The survival and growth of bacteria, such as Legionella, Mycobacterium, and Aeromonas,

under limited nutrient conditions of water distribution systems, is also of concern because of

potential risks that may be associated with inhalation, ingestion, or dermal exposure. The

maintenance of a disinfectant residual is not always effective in preventing the survival and growth

of bacteria within a distribution system, and defining criteria for biologically stable drinking water

is important to prevent potential risks of infection from these or other microorganisms. Research

has shown that Legionella proliferation can be controlled in potable water by interfering with the

Legionella-protozoan receptor site interaction.
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Distribution systems represent the final link in the chain between raw source water,

treatment facilities and the consumer. However they are generally designed and operated to

satisfy hydraulic reliability objectives -- providing adequate water quantity and pressure for fire

flow, and domestic, commercial and industrial demands -- rather than to maintain water quality. 

This frequently results in large service mains, dead-end branches, and large storage facilities

which keep water in the system for long periods of time, leading to degradation of water quality.

Individual distribution systems contain hundreds and even thousands of miles of pipe. As

water flows through this pipe and sits in storage reservoirs, reactions can take place between

constituents within the water itself and with materials along the wall of the pipe and reservoir. 

The distribution system is thus a giant chemical reactor, with residence times far in excess of those

seen within a treatment plant.

The complex, looped nature of the piping network, in some systems, the presence of

multiple sources of water feeding the system, the fill-and-draw operation of storage facilities and

variable water usage rates at different locations and times of the day create very complex flow

patterns. These patterns often defy any intuitive sense of where water is traveling at any given

point in time. Such flow patterns combined with time spent in storage contributes to residence

times that can exceed several days. The result, as verified by field surveys, is that water which left

a treatment plant with a very uniform level of quality, can exhibit a highly variable pattern of

water age and quality in both time and space throughout a distribution system. Some of the

negative impacts of time spent by water in a distribution system include loss of disinfectant

residual, growth of disinfection by-products, growth of biofilm colonies along pipe walls, and the

protection and subsequent release of nuisance and pathogenic organisms from the biofilm over

time. 

External contamination of water flowing in the distribution system is an ever-present

threat to public health and has been shown to be the most frequent cause of waterborne disease

outbreaks. There is growing evidence that endemic and epidemic waterborne disease is

associated with breaks in the integrity of distribution lines, cross-connections and other breaches

of distribution system integrity. Research is needed to improve the design, construction,

rehabilitation, operation, and maintenance of distribution system integrity. As pipe ages and
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corrodes it exerts a higher chlorine demand and provides more environmental niches for biofilm

protection and proliferation. Many water distribution systems in this country are approaching

100 years old. An estimated 26% of distribution system pipe is unlined cast iron and steel and is

in poor condition. At current replacement rates for distribution system components, a utility will

replace a pipe every 200 years.

The volume available in storage facilities is often several times that of the pipes in the

distribution system. The degree to which water is well mixed within these facilities is largely

unknown, as is the possible impacts of discharging extremely old water from unmixed zones under

conditions of high demand. Guidelines on how to design and operate storage facilities to promote

better mixing are needed.

Most medium- and large-scale utilities employ sophisticated data acquisition systems for

monitoring and controlling the hydraulic performance of their distribution systems. The methods

and benefits of extending these systems to include water quality parameters should be studied. 

There is currently no consensus in the water industry on the relative effectiveness of pipe cleaning

versus pipe repair or replacement for enhancing water quality. The same can be said for

identifying effective institutional programs for implementing cross-connection and backflow

prevention programs.

For the past decade or more, extensive field studies have been conducted characterizing

the chemical changes occurring in drinking water in distribution systems and identifying biofilm

growth along pipe walls. EPA has developed a sophisticated computer model that tracks the fate

of chemical species in complex pipe networks and are currently used by utilities and engineers

throughout the world (EPANET). EPA has also developed methods for determining organic

carbon available to support biofilm growth and has developed guidebooks for controlling such

growth in distribution systems.

Microorganisms are known to colonize the walls of pipe in the form of thin biofilms. The

negative impacts of such biogrowth, particularly with regard to harboring and breeding

pathogens, requires more study. Research is also needed to determine the proper combination of

nutrient reduction and disinfectant level to control biofilm growth under site-specific conditions.
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The AWWA Research Foundation has supported studies examining the kinetics of

chlorine consumption in distribution systems and the factors limiting microbial growth. The

National Water Research Institute is funding research to understand the microbial interactions

within biofilms. French researchers at N.A.N.C.I.E. have been operating a full-scale distribution

system simulator for several years. They have quantified the effects of pipe material, biological

seed concentration and disinfectant choice on biofilm formation. Researchers at Lyonnaise des

Eau have studied the factors contributing to chlorine demand from the pipe wall and have

developed a chlorine microsensor that can be placed at the pipe wall. At least one water authority

in the UK is experimenting with on-line sensing of water quality conditions within distribution

systems and is developing a biofilm monitor.

Research studies indicate the need for more accurate kinetic models that can simulate the

loss of chlorine, the formation of disinfection by-products and the growth of microorganisms in

distribution systems. Research is also needed to identify the factors that affect the growth of

biofilms and the survival of opportunistic pathogens in distribution systems. There is also strong

evidence of the interactions between treatment and regrowth of bacteria in the distribution system. 

These studies indicate the need to conduct research on the potential for modifying treatment to

control the formation of biofilm and the survival of pathogens. 

Research Topics and Priorities

Priorities were assigned on the following basis: Due to the growing evidence that endemic

and epidemic waterborne disease is associated with breaks in the integrity of distribution lines,

cross-connections and other breaches of the distribution system integrity, all projects addressing

the cause of microbial intrusion into the distribution system and corrective actions are rated high

priority. Until it has been established that heterotrophic bacteria pose a health risk and that

present disinfection practices may be inadequate to prevent an unacceptable risk, projects

proposed which are related to microbial quality are assigned a medium priority. The only other

distribution system projects in this section of the plan which were considered a high priority are

those which will provide information for disinfection by-product risk assessment modeling, i.e. the

kinetic models for chlorine decay, DBP formation and the enhancement of the EPANET model.

a. Use of coliforms (or other surrogates) to indicate adequate control of primary and
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opportunistic pathogens in biofilms and pipe sediments 

Coliforms are used to determine the sanitary quality of drinking water. If opportunistic

pathogens are found to pose significant risks, additional research in this area will be needed to

assess the use of coliforms as surrogates.

 RM.M.14- Bacteria interference with detection of coliforms and E. coli 

The presence of high densities of bacteria is known to interfere with assays for total

coliforms, the current basis for regulating the microbial quality of drinking water. 

Research is needed on issues such as interference with the presence-absence approach to

coliform monitoring.

Priority: Medium

b. Water quality factors affecting biofilm growth and the effectiveness of disinfectant

residuals in controlling growth

 RM.M.15- Kinetic Models for chlorine decay in distribution systems

Using laboratory and field studies, alternative kinetic models for chlorine decay in

distribution systems are being evaluated. Reactions of chlorine at the pipe wall can be

very important in some systems and can be correlated to hydraulic roughness coefficients. 

This work is being performed in association with AWWARF, Montgomery Watson, and

Lyonnaise de Eau.

Priority: Completed

RM.M.16 - Enhancement to the EPANET distribution system water quality model 

(Ongoing) A new version of EPANET, a program that models water quality fate and

transport in distribution systems, is being developed. It incorporates new kinetic models

for chlorine decay and THM formation, variable geometry storage tanks with incomplete

mixing, and more flexible operational rules for specifying system operation. 

Priority: High

RM.M.17 - Preliminary studies of biofilm formation rates in pilot scale distribution

systems (Ongoing) Study of the factors affecting the rate of biofilm growth on pipe walls

using a pilot-scale distribution system is beginning. The pilot system consists of multiple
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recirculating loops of 6" pipe with removable biofilm coupons inserted in the wall. Initial

experiments will compare biofilm growth rates under different chlorine levels. This will

expand to compare rates under alternative disinfectants and nutrient control strategies. 

Priority: Medium

RM.M.18 - Opportunistic pathogens in biofilms Identify the prevalence of

opportunistic pathogen growth in biofilms and develop mitigation measures.

Priority: Medium

RM.M.19 - Impact of nutrient removal on growth potential for bacteria Pilot studies

are being conducted on removal of nutrients from treated drinking water. Pilot-scale pipe

loop studies will be conducted to evaluate growth potential for bacteria in distribution

systems. 

Priority: Medium

RM.M.20 - Impact of alternative treatment on biofilm growth Assess the potential

of alternative treatment systems to promote biofilm growth in the distribution system,

using a pilot-scale distribution system. 

Priority: Medium 

RM.M.21 - Water quality factors in distribution systems (Ongoing) Studies are

underway to investigate the importance of biofilm development and microbial interactions

on the beneficial and detrimental processes in drinking water distribution systems. One

aspect of this research addresses the interactions between pipe materials, corrosion

inhibitors, disinfectants, organics, and distribution biofilms. A second effort addresses online monitoring of pathogen ecology for quantitative evaluation of mitigation procedures.

Priority: Medium

See also RM.M.26 - Bacterial growth in distribution systems

c. Effect of design and condition of the distribution system on bacterial growth
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Additional characterization studies are needed to identify points in the distribution system

that are particularly vulnerable to degradation of water quality. The first candidates for study are

dead-end locations, for which there is a dearth of long-term data. Studies have shown that up to

25% of drinking water consumers drink their water from dead-end sections of the distribution

system. Additional knowledge is needed on the role that storage facilities play in influencing

water quality changes. The long detention times in such facilities can reduce disinfectant residual

but might also reduce the nutrients that promote biofilm growth. Further study is needed on how

to design a tank to promote uniform mixing within it. Guidelines on size and location of influent

and effluent lines to accomplish this goal are needed.

Computer modeling needs to be enhanced to accommodate the effect that mixtures of

treated source waters have on kinetic coefficients that model the decay of chlorine or growth of

by-products. More fundamental kinetic models of by-product formation need to be developed

that take into account the concurrent loss of disinfectant and production of multiple species of byproducts. The same can be said for modeling the complex chemistry of chloramines when used as

a disinfectant. 

Improved information management can help shift the emphasis in distribution system

operation towards a better blend of public health and hydraulic reliability objectives. Advances in

remote sensing and data acquisition technologies applied to the specific needs of the water utility

industry can make system operators more aware of current water quality conditions within their

system and help them make short-term decisions to improve its quality (e.g., disinfectant doses,

tank fill/release rates, and pump control strategies).

RM.M.22 - Water quality impacts of dead ends Examine the water quality impacts of

dead ends. Conduct continuous, long-term monitoring of water quality conditions such as

coliform, chlorine residuals and corrosion by-products at dead-end branches and loops of

a distribution system.

Priority: Medium

RM.M.23 - Mixing in storage facilities Study mixing in storage facilities, including the

factors affecting mixing and residence times in distribution system storage facilities. 
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Develop guidelines for maintaining well-mixed conditions.

Priority: Medium 

RM.M.24 - Alternative kinetic models for decay and DBP formation Develop multicomponent kinetic models for disinfectant residual decay and formation of selected DBPs

in distribution systems. 

Priority: High

RM.M.25 - Real-time monitoring systems Study real-time data acquisition and control. 

Demonstrate monitoring of water quality variables in real-time and use to modify

distribution system operation to maintain good water quality.

Priority: Medium

Other projects which also address this topic:

RM.M.30 Opportunistic pathogens in biofilms

d. Effect of filtration/disinfection treatment processes on chemical and biological stability of

water in distribution systems

Future research will continue to emphasize the role that biofilm development along pipe

walls plays in posing risks to public health. Both a better biological and chemical engineering

understanding of the structure and growth dynamics of biofilms are needed in order to develop

effective control programs, some of which may involve treatment decisions at the water treatment

plant. In particular, the degree to which treatment technologies minimize nutrient 

availability in the treated water will affect subsequent growth of bacteria in the distribution

system.

RM.M.26 - Bacterial growth in distribution systems Quantify the factors affecting the

growth of biofilm on pipes, and identify effective control strategies.

Priority: High 
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RM.M.27 - Integrated approaches for controlling pathogens Characterize the

interactions among treatments on the microbial quality of water in distribution systems. 

Interactions of concern include effects of corrosion control, loss of residual disinfectants

and GAC for DBP control on microbial quality. 

Priority: Medium

e. Maintaining Distribution System Integrity

Microbial pathogens, and other contaminants can enter the distribution system in many

ways including: piping failure, construction activities, repair and maintenance operations, back

pressure, sewage cross-connections, poor system design, and poor operational practices. As we

move toward the 21 century, greater attention will have to be given to design, operation and st

maintenance of distribution systems to ensure water quality as well as hydraulic reliability. This

will include consideration of advanced materials of construction as well as installation of sensors

for real-time monitoring of important distribution system quality indicators such as disinfectant

residuals, water pressure, flow direction, microbial densities, total organic halides, and other

quality parameters.

RM.M.32 - Evaluate the primary causes of leaks and failures in water distribution

systems There is increasing concern over the potential deterioration of drinking water

distribution system components and evidence exists that, especially in the largest urban

areas in the U.S., this deterioration is well underway. Recent boil water orders and MCL

violations in New York City and Washington D.C. support this concern. This task will

support a coordinated effort with organizations such as the American Water Works

Association Research Foundation, the American Public Works Association, the Civil

Engineering Research Foundation, the Water Environment Federation Research

Foundation, the Cross Connection Control Association, and the Association of State

Drinking Water Administrators to determine the primary causes of leaks in distribution

systems. 

Priority: High

RM.M.33 - Evaluate state-of-the-art devices for determining the structural integrity
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of water distribution systems Research will be conducted on state-of-the-art technology

that can be used to establish the structural integrity and reliability of drinking water

distribution system components. For example, sensors that can be used to provide

acoustic leak detection capability or that can be imbedded into system components to

predict component failure and to establish structural integrity will be investigated. Remote

monitoring techniques and telemetry will be investigated to measure real-time water

quality in distribution systems and indicate integrity and reliability of distribution system

components.

Priority: High

RM.M.34 - Evaluate materials for constructing distribution system components 

Many materials in common use in drinking water distribution systems are subject to

corrosion and failure under stress. These failures can range from leaks to catastrophic

failure. This task will examine the potential for the use of new construction material that

can resist the common mechanisms of failure in pipelines. For example, stainless steel is

now being evaluated for use in drinking water systems in Japan. Stainless steel is resistant

to corrosion, is flexible and has a long structural life.

Priority: High

3. How can source water be protected to ensure that it is consistent with finished water

quality of acceptable microbial risk after appropriate treatment?

State of the Science

Passage of the 1996 Amendments of the Safe Drinking Water Act has focused the

attention of water utility mangers and public health and regulatory officials on source water

protection and its role in protecting public water supplies. There is growing awareness that water

treatment and /or disinfection may not always be adequate to ensure the provision of potable and

safe water to the consumer. The cryptosporidiosis outbreak in Milwaukee, Wisconsin has raised

the possibility that even water suppliers which meet all of the Surface Water Treatment Rule

(SWTR) requirements are vulnerable. In the Milwaukee case more then 400,000 illnesses and as

many as 100 deaths were associated with the outbreak. The cause of the outbreak was attributed
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to a combination of poor treatment operations and a sudden increase in source water turbidity

resulting from a wet weather flow event. This and other similar but less dramatic waterborne

outbreaks has spurred an interest in assessing the occurrence of protozoan cysts in source and

treated water. This research activity is closely related to ongoing research being conducted under

NRMRL’s Wet Weather Flow (WWF) Program. The WWF Program is examining techniques for

characterizing WWF events, and for development of Best Management Practices for controlling

the impact of WWF events on water quality in receiving streams. For example these studies will

characterize the factors that influence the overland flow of pathogens such as Cryptosporidium,

and evaluate the effectiveness of end-of-the-pipe control technologies and on-site waste water

treatment technologies. This project will also utilize results from projects currently being funded

by the AWWARF and WERF. 

Research Topics and Priorities

a. The impact of source water protection on the performance of drinking water treatment

systems

Areas of potentially productive risk management research are as follows: development and

calibration of GIS techniques for describing source water characteristics; development,

application and calibration of new and existing water quality models (BASINS); and defining the

factors that influence the performance of conventional treatment when concentration of

contaminants in source water increases rapidly. Given the current emphasis on source water

protection in the 1996 Amendments to the Safe Drinking Water Act, all of these activities are

categorized as high-priority research.

Task RM.M.35 - Evaluate GIS techniques for defining source water characteristics 

GIS techniques have become widely used for integrating and displaying land use data for

watersheds and river basins. This tool is very effective for visually displaying and

integrating various types of data bases that can lend insight into the factors that influence

watershed functions. For example, GIS have been used in the Ohio River Basin to show

the relative location of water supply intakes, dams and waste water and industrial

discharges on the Ohio River using EPA’s REACH file as an integrator. However, little
3-53

has been done with integrating GIS and functional models to predict the behavior of the

watershed and its impact on water quality. For example GIS, soil moisture vegetative

cover and atmospheric models can be used to predict the types and severity of wet

weather flow events that may be expected to take place in a given type of watershed. This

information can be used to understand and characterize the effects of point, and non-point

source run off on ground water surface water interactions and on surface and ground

water quality. There are many existing data bases available through agencies such as the

Corps of Engineers, the USGS and the USEPA that can be utilized to provide basic data

input for this type of analysis. This task will evaluate existing data bases and models that

can be integrated with GIS to provide information that could be used to define the

characteristics of watersheds and show how these characteristics influence water quality in

rivers, streams and the subsurface. 

Priority: High

Task RM.M.36 - Evaluate water quality models for routing point and non-point

source water discharges Water quality models can be used to provide the linkage

between wet weather flow events and water quality in drinking water sources. The

U.S.EPA, the COE, along with other government agencies, academia and the private

sector have invested a great deal of resources in developing and distributing hydraulic and

water quality models for use in river basins and watersheds. This task will examine and

evaluate these models and make recommendation as to which are most appropriate for use

in specific types of circumstances. Issues related to field calibration, types of input data

required, and ease of use will be investigated. This project will also address the

relationship between best management practices as evaluated in our Wet Weather Flow

program and their impact on protecting source waters for drinking water purposes.

Priority: High

Task RM.M.37 - Evaluate the impact of sudden increases in source water

contaminant concentration on drinking water treatment There is increasing evidence

that drinking water unit processes are vulnerable to sudden increases in contaminant

concentration in raw water. The Milwaukee cryptosporidiosis outbreak was in part due to
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the effect of a wet weather flow event that resulted in sudden and unexpected increases in

turbidity in the source water. This wet weather flow event in combination with poor

treatment operations resulted in the largest recorded waterborne disease out break in the

history of the U.S. There is other, although less dramatic, information that sudden

changes in contaminant concentration will degrade the effluent quality of treated water. 

This task will investigate the design and operating variables that influence water treatment

systems. Research will be conducted to define the conditions that cause water treatment

systems to fail under the influence of rapidly increasing raw water contaminant

concentrations. 

Priority: High
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Table III-2

Research Priorities for Health Effects of Microbial Pathogens

Research Topics

a. Pathobiology of infection HE.M.1 - Infectious dose of Cryptosporidium High

and disease for the most HE.M.2 - Validity of d-r model for High

important waterborne Cryptosporidium

pathogens HE.M.3 - Cryptosporidium virulence study High

HE.M.5 - Infectious dose of Norwalk virus High

b. Characterization of HE.M.7 - Characterization of endemic disease High

epidemic and endemic HE.M.8 - Immunological assays for use in High

waterborne disease epidemiology studies

HE.M.4 - Cryptosporidium infectious High

dose/immunity

HE.M.6 - Infectious dose of other pathogens Medium

HE.M.9 - Investigation of waterborne outbreaks High

HE.M.10 - Surveillance tools for outbreaks High
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Table III-3

Research Priorities for Exposure to Microbial Pathogens

Research Topics Proposed Projects Priorities

Microbial Methods

a. Methods for detecting and EX.M.1 - Immunological techniques for protozoa High

enumerating Cryptosporidium EX.M.2 - Gene probes for detection of viable High

and Giardia (including Cryptosporidium oocysts

identifying the viability EX.M.3 - Cultural method for Cryptosporidium in High

potential) in source and environmental samples

finished drinking water, and EX.M.4 - PCR methods for Giardia and Medium

methods for other emerging Cryptosporidium

protozoa EX.M.5 - Protozoa methodology protocol development High

b. Methods for detecting and EX.M.8 - Application of PCR technologies and gene Medium

enumerating viruses in source probes for virus detection in water

and finished drinking waters EX.M.9 - Norwalk virus High

workshop

EX.M.6 - Comparison of methods for Giardia and High

Cryptosporidium in water

EX.M.7 - New protozoa agents High

EX.M.10 - Methods for emerging viruses High
3-57

Microbial Exposure

a. Surveys to determine EX.M.11 - Intensive evaluation of microbiological High

pathogen occurrence in constituents and treatability in surface source waters

source and finished waters EX.M.12 - Identification of viruses resistant to Medium

b. Importance of watershed EX.M.13 - Distinguish animal versus human sources High

control (including point

source, non-point source, and

septic tank controls) for

source water pathogen EX.M.14 - Occurrence of Mycobacterium High

occurrence EX.M.15 -Occurrence of heterotrophic bacteria with High

c. Occurrence of and EX.M.16 - PCR method for Legionella Low

exposure to primary and EX.M.17 - Pathogenicity of heterotrophic bacteria found High

opportunistic pathogens in in drinking water

distribution systems EX.M.18 - Occurrence of opportunistic pathogens in Medium

disinfection. 

virulence characteristics

biofilms

EX.M.19 - Opportunistic pathogens associated with Medium

point-of-use (POU) and point-of-entry (POE) filter

effluents

EX.M.20 - Potential pathogenicity of heterotrophic Medium

bacteria from POU filters

EX.M.21 - Occurrence of newly emerging pathogens High

EX.M.22 - Exposure as a function of population High

distribution
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Microbes in Groundwater 

a. Survival and transport of EX.M.23 - Virus survival in the subsurface High

pathogens in the subsurface EX.M.24 - Virus transport in the subsurface High

b. Methods for protecting EX.M.25 - Viral transport and fate models Medium

wells and springs from EX.M.26 - Vulnerability of ground water to pathogens High

pathogens EX.M.27 - Delineation of natural protection zones Medium

EX.M.28 - Vulnerability & sensitivity analysis High

EX.M.29 - Occurrence of Clostridium perfringens High

EX.M.30 - Aquifer well mapping Medium

EX.M.31 - Correlation of water age and microbial High

viability

EX.M.32 - Septic Tank Siting High

EX.M.33 - Virus sampling and phage research High
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Table III-4

Research Priorities Risk Assessment for Microbial Pathogens

Research Topics Proposed Research Priority

a. Modifications of risk assessment RA.M.1 - Development of a comprehensive High

paradigm for characterizing microbial microbiology risk assessment model for

risks water. 

b. Accuracy of dose response models in RA.M.2 - Evaluation/Application of High

predicting waterborne disease various dose-response relationship models.

c. Characterization of risks posed by RA.M.3 - Evaluation and application of Medium

exposure to multiple or complex issues and methods to assess risk associated

mixtures of pathogens with exposures to multiple pathogens,

routes, disease course and outcomes, and

durations.
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Table III-5

Research Priorities for Risk Management of Microbial Pathogens

Research Topics Proposed Research Priority

Pathogen Removal

a. Optimization of conventional RM.M.1 - Filtration studies for controlling pathogens High

treatment processes to remove RM.M.2 - Filtration removal of protozoa and indicators High 

pathogens RM.M.3 - Optimize conventional treatment for removal of High 

oocysts 

RM.M.4 - Filtration damage viability studies High 

RM.M.5 - Evaluate disinfection in field-scale treatment plants High 

RM.M.28 - Evaluation of the effectiveness of conventional Medium

treatment processes on removing and inactivating emerging

pathogens

b. Effectiveness of different RM.M.6 - Biological treatment for control of oocysts High

filtration processes in removing RM.M.7 - Filtration techniques other than conventional Medium

pathogens treatment

RM.M.29 - Evaluation of different filtration processes on Medium

removing emerging pathogens

c. Effectiveness of disinfection RM.M.8 - Control of Norwalk virus by chlorine and ozone High 

processes in inactivating RM.M.9 - UV disinfection efficiencies for Norwalk viruses High

pathogens RM.M.10 - Inactivation of Giardia and Cryptosporidium by High 

sequential disinfectants

RM.M.30 - Evaluation of alternative inactivation processes for High

controlling viruses

RM.M.31 - Evaluation of different disinfection processes in Medium

inactivating emerging pathogens

d. Appropriateness and costs of RM.M.11 Cryptosporidium removal using bag filters High 

technologies for small systems RM.M.12 - Cost-effectiveness of prefiltration for ultrafiltration High

unit 

RM.M.13 - Development/testing of innovative technologies for High 

small systems
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Distribution systems

a. Use of coliforms (or other RM.M.14 - Bacteria interference with detection of Medium

surrogates) to indicate coliforms and E. coli

adequate control of primary

and opportunistic pathogens

in biofilms and pipe sediments

b. Water quality factors

affecting biofilm growth and RM.M.15 - Kinetic Models for chlorine decay in Completed

the effectiveness of distribution systems

disinfectant residuals in RM.M.16 - Enhancement to the EPANET distribution High 

controlling growth water quality model

c. Effect of design and

condition of the distribution RM.M.22 - Water quality impacts of dead ends Medium 

system on bacterial growth RM.M.23 - Mixing in storage facilities Medium 

d. Effect of

filtration/disinfection RM.M.26 - Bacterial growth in distribution systems High 

treatment processes on RM.M.27 - Integrated approaches for controlling Medium

chemical and biological pathogens

stability of water in

distribution systems

RM.M.17 - Preliminary studies of biofilm formation rates Medium

in pilot-scale distribution systems

RM.M.18 - Opportunistic pathogens in biofilm Medium

RM.M.19 - Impact of nutrient removal on growth Medium

potential for bacteria

RM.M.20- Impact of alternative treatment on biofilm Medium

growth

RM.M.21 - Water quality factors in distribution systems Medium

RM.M.24- Alternative kinetic models for decay and DBP High 

formation

RM.M.25- Real-time monitoring systems Medium
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Distribution systems (Cont.)

e. Maintaining Distribution

System Integrity RM.M.32 - Evaluate the primary causes of leaks and High

Source water

a. The impact of source water

protection on the performance RM.M.35 - Evaluate GIS techniques for defining source High 

of drinking water treatment water characteristics

systems RM.M.36 - Evaluate water quality models for routing High

failures in water distribution systems

RM.M.33 - Evaluate state-of-the-art devices for High

determining the structural integrity of water distribution

systems

RM.M.34 - Evaluate materials for construction High

distribution system components

point and non-point source water discharges

RM.M.37 - Evaluate the impact of sudden increases in High

source water contaminant concentration on drinking water

treatment
4-1

CHAPTER IV. RESEARCH FOR DISINFECTION BY-PRODUCTS

A. BACKGROUND

Public health concern over the disinfection process was first raised over 20 years ago with

the identification of chloroform and other trihalomethanes (THMs) in chlorinated drinking water. 

Since that time, over 100 chemical by-products of the disinfection process have been found in

treated drinking water. Based on several studies, the most prevalent chlorination by-products by

weight are the total THMs (TTHMs), followed by the haloacetic acids (HAAs), chloral hydrate,

haloacetonitriles, haloketones, and chloropicrin. Between 20% and 60% of the halogenated

material resulting from chlorination are accounted for by these compound classes. The

concentrations of the chlorination by-products depend on several factors, with the total organic

carbon (TOC) level (a surrogate for the amount of precursor material) in the water being the most

important. In addition, the concentrations of chlorinated by-products are generally higher in

surface waters than ground waters because the level of TOC is higher in surface waters.

The concentrations of the TTHMs and HAAs likely comprise more than 50%, on a weight

basis, of the aforementioned halogenated by-products that have been identified in drinking water. 

Based on the model used in the proposed Stage 1 DBP rule to predict occurrence of TTHMs and

HAAs in systems serving greater than 10,000 people and using surface water, the median

concentration of TTHMs nationally is 45 Fg/l with a 95th percentile of 104 Fg/l (the proposed

Stage 1 Maximum Contaminant Level (MCL) for TTHMs is 80 Fg/l). Of the THMs, chloroform

generally occurs in the highest concentrations, but the brominated and bromochloro- compounds

are found in the highest concentrations in high bromide waters. For HAAs, the model predicted

that the median concentration for the sum of five of the HAAs nationally is 27 Fg/l with a 95th

percentile of 86 Fg/l (the proposed Stage 1 MCL for the HAAs is 60 Fg/l). Of the HAAs,

dichloroacetic and trichloroacetic acid generally have the highest concentrations, but the

brominated and bromochloroacetic acids occur in the highest concentrations in high bromide

waters. The other chlorination by-products generally occur at levels less than 10 Fg/l.

Chloramines react to form chlorine-containing by-products, but generally at significantly
4-2

lower levels than does chlorine. When free chlorine is present during the application process, the

level of chlorine-containing by-products increases. Chloramination also produces nitrogencontaining by-products, such as cyanogen chloride and organochloramines. Cyanogen chloride

generally occurs at concentrations < 5 Fg/l (Stage 1 does not propose an MCL for cyanogen

chloride).

The disinfectant chlorine dioxide does not react to form significant levels of chlorinecontaining organic by-products, but chlorine dioxide has been found to produce the inorganic byproducts, chlorate and chlorite. Limited data suggest that chlorite and chlorate are expected in

concentrations between 0.5 to 1.5 mg/L and 0.1 to 0.5 mg/L, respectively (the proposed Stage 1

MCL for chlorite is 1.0 mg/L; an MCL is not proposed for chlorate).

Relative to chlorination, considerably less is known about by-products of ozonation. The

most prevalent ozone by-products are aldehydes, ketones, carboxylic acids, ketoacids, and

hydrogen peroxide. Bromate, bromoform, and dibromoacetic acid are formed in high bromide

waters. The available health and exposure data for these by-products suggest that bromate is of

greatest concern. The nationwide distribution of bromate occurrence in surface waters using

ozone for pre disinfection has been roughly estimated as a median of 1 to 2 Fg/l and a 90th to

95th percentile in the range of 5 to 20 Fg/l (the proposed Stage 1 MCL for bromate is 10 Fg/l).

This chapter describes proposed research for DBPs in the areas of health effects,

exposure, risk assessment and risk management. The major research questions in each area are

summarized in Table IV-1. For each question, the state of the science, research needs and

proposed research projects are described.
4-3

Table IV.1 - Major Research Questions for Disinfection By-Products

Health Effects

1. What are the health effects associated with exposure to DBPs?

1.1 What are the health effects in communities served by disinfected drinking water?

1.2 What is the toxicity of individual chemical contaminants and of mixtures of DBPs?

Exposure

1. What methods are needed for measuring occurrence of DBPs in drinking water?

 2. What levels of DBPs are people actually exposed to via their drinking water supplies,

and what is the population distribution of exposures?

Risk Assessment

 1. How can we characterize the risk posed by exposure to specific and multiple or

complex mixtures of DBPs in drinking water?

 2. How can the risks from chemicals and microbes be compared?

Risk Management

 1. How effective are various treatment processes in minimizing the formation of DBPs?

B. HEALTH EFFECTS RESEARCH

1. What are the health effects associated with exposure to DBPs?

Information on the health effects of DBPs from both epidemiology and toxicology studies

is currently inadequate for conducting comparative assessments of the potential cancer and

noncancer risks posed by the use of chlorine, chloramine, ozone, chlorine dioxide, or

combinations of these disinfectants. The anticipated increased use of alternatives to chlorine in

the future underscores the need to assign a high priority to research that will permit a better

characterization of the risks that may be associated with exposure to the by-products of these

alternatives. The toxic effects of many DBPs, particularly those associated with the use of
4-4

disinfectants other than chlorine, are unknown or poorly characterized. Beyond the need for basic

toxicologic data, an improved understanding of the chemical, physical and biological processes

involved in the toxic response is critical for evaluating the human risk associated with exposure to

these contaminants. Improved estimates of exposure and health must be utilized in future

epidemiology studies so that the public health risks to communities served by disinfected drinking

water may be characterized with a reasonable degree of confidence.

The criteria listed in Chapter I were used to select and prioritize research projects. As an

iterative research plan, priorities are likely to change as the results of ongoing research and

information about emerging problems become available. This is a particularly important issue

with respect to the planning of health research to assess the risk associated with exposure to

DBPs. The current research plan emphasizes the need for feasibility studies to determine if fullscale epidemiology studies are likely to provide better estimates of cancer and reproductive risks

than those derived from previous studies. In the event that full-scale studies are not conducted,

risk assessors will place a greater reliance on the use of animal toxicity data for individual DBPs. 

This will necessitate an enhanced program to improve the scientific basis for extrapolating animal

toxicity data to humans. Under this scenario, research on toxic mechanisms and pharmacokinetics

will receive considerably more emphasis. Priorities for health research on individual DBPs will

also be influenced by the ability of mixtures research to address the overarching question of

drinking water health risks from consumption of disinfected water. 

The 1996 SDWA Amendments assign a high priority to the types of research activities

described below, emphasizing the need for toxicology and epidemiology research to evaluate the

cancer and reproductive risks that may be associated with exposure to DBPs resulting from

different disinfectants. The Amendments also place a priority on research to understand the

mechanisms by which DBPs cause their effects (cancer and noncancer), the risks posed by

complex mixtures of contaminants, and the factors that influence effects in the general population

and in susceptible groups.
4-5

1.1 What are the health effects in communities served by disinfected drinking water?

State of the Science

The identification of potentially carcinogenic DBPs such as chloroform in drinking water

two decades ago prompted a number of epidemiology studies to evaluate cancer risks in

communities served by chlorinated drinking water supplies. These studies have primarily involved

comparisons of populations consuming chlorinated surface water or unchlorinated ground water. 

Some investigations have shown no associations between consumption of chlorinated water and

cancer, while others have suggested weak to moderate associations with cancers of the colon,

rectum and bladder (collectively, up to 10,000 cases annually). In general, the risk estimates

derived from these studies are highly uncertain due to problems with study design,

characterization of exposures and ascertainment of health effects. Recent studies in Iowa and

Canada have provided additional weight-of-evidence for the association between exposure to

chlorinated by-products and the risk of cancer. Epidemiology studies to investigate the possible

association between DBP exposures and adverse reproductive outcomes have similarly not

provided conclusive evidence of causality, but they have been useful for generating hypotheses

and identifying research needs. The high priority given to epidemiology research in this plan is

responsive to the need to address these important public health concerns.

Obtaining reliable estimates of exposure in cancer studies has been particularly

problematic due to the need to reconstruct historical exposures that may span several decades

back in time. Additionally, most epidemiology studies to date have relied upon either TTHMs or

chloroform as surrogates for exposure to the complex mixture of DBPs in water. Recent studies

have demonstrated that THMs as a class or individually may not adequately predict exposure to

other types of DBPs. It is now recognized that the relative concentrations of the individual THMs

in a given water supply, and their relative toxicities in animal tests, vary considerably. 

Furthermore, other types of by-products may be of greater concern from a health perspective. 

For example, recent toxicologic data suggest that of all the DBPs for which data exist,

dibromoacetic acid is perhaps the most potent male reproductive toxicant in rodents. Levels of

this DBP and other toxicologically important brominated by-products, including
4-6

bromodichloromethane (primarily a chlorination by-product) and bromate (an ozonation byproduct), are greater in communities where bromide concentrations in the source water are high. 

These concerns highlight the importance of selecting the appropriate marker(s) of DBP toxicity to

use in both cancer and reproductive outcome epidemiology studies.

Health data in cancer epidemiology studies have commonly been obtained from cancer

mortality rates, death certificates, or interviews. The variable quality of information obtained by

these measures and the potential problems in associating exposures to cases are important

uncertainties that need to be addressed in future cancer studies. With respect to adverse

reproductive effects, the few existing studies have focused on a limited range of health outcomes

(fetal development and selected congenital malformations). To comprehensively address this

issue, studies need to include an examination of measures of fecundity and fertility in both males

and females. Future epidemiology studies to address these health issues clearly need improved

assessments of exposure and health effects, enhanced coordination with animal toxicology

research to ensure emphasis on the most appropriate endpoints and markers of exposure, and

greater emphasis on interdisciplinary approaches in the field.

EPA has used a three-step strategy to define the critical issues in human health research

for both cancer and reproductive endpoints: 1) sponsor expert panel workshops to discuss the

available data, determine if additional epidemiology research can improve the state of the science,

and if so, obtain guidance on research approaches and priorities; 2) conduct methods development

and feasibility studies, with consideration of the recommendations of the expert panel; and 3)

conduct full-scale studies, depending upon the outcome of the feasibility studies.

EPA has conducted expert panel workshops (step #1) for both cancer and reproductive

endpoints. The cancer workshop panel recommended conducting feasibility studies to identify

geographic locations with adequate exposure data and appropriate cohorts for study (including

the possibility of using existing cohorts that are being studied for other potential exposures). 

Several possible designs for full-scale studies (i.e., cohort, case-control, and case-control nested

within a cohort) were suggested. The panel recommended research on biomarkers of exposure,

effect, and susceptibility, and strongly encouraged research to improve exposure assessment for
4-7

epidemiologic studies. The recommendations of the cancer workshop panel with respect to

assessment activities are discussed in the Risk Assessment section of this chapter.

In 1993, EPA and the International Life Sciences Institute (ILSI) convened an expert

panel to review the published epidemiologic and experimental data on reproductive and

developmental effects, and to develop a strategy for related short-term and long-term research. 

The panel concluded that the current available data on the effects of chlorination by-products

provide an inadequate basis for identifying DBPs as a reproductive or developmental hazard. 

Recommendations were made for refining studies using existing data bases, strengthening studies

designed to collect new data, improving exposure assessments, investigating selected health

endpoints, and developing a stronger link between animal research and epidemiology studies (e.g.,

laboratory development and field testing of biomarkers). EPA subsequently conducted a one-day

workshop in March of 1995 to review ongoing laboratory and field research on reproductive and

developmental effects of DBPs. Participants discussed directions for future research in this area,

and reiterated several of the general conclusions of the 1993 workshop. In July of 1997, EPA

convened an expert panel to review the existing reproductive epidemiology data base and to

develop recommendations for future research.

Current Epidemiology Studies Current DBP epidemiology research in the U.S. is focused

primarily on evaluations of the of the possible associations between exposure to by-products and

the risks of adverse reproductive outcomes. Two epidemiology studies of adverse reproductive

outcomes are being conducted in New Jersey. One is using improved methods for estimating

exposures to test the findings of earlier studies in that state in which neural tube defects were

associated with elevated levels of THMs, nitrates, and solvents. The second is a cross-sectional

study of public drinking water contamination and birth outcomes in various counties in New

Jersey, using ambient levels of THMs and selected solvents as markers of exposure. The State of

California is evaluating possible associations between individual or TTHMs in residential drinking

water and adverse pregnancy outcomes, including spontaneous abortion, low birth weight,

preterm delivery and intrauterine growth retardation. Finally, a pilot study using a geographic

information system and water quality modeling is evaluating the relationship between birth weight

and exposure to DBPs. This EPA-funded project is listed below under the section
4-8

"Development/application of improved tools for field research." The results of all of these studies

should be available in 1997. 

Research Topics and Priorities

The following research addresses many of the recommendations of the participants in the

cancer and reproductive effects workshops, as described in the State of the Science section above. 

These projects are all highly ranked because they address potential risks of greatest concern for

DBPs in drinking water (cancer and adverse reproductive outcomes), and if successful, they will

significantly reduce uncertainties in the current risk assessments and will lead to more scientifically

sound, cost-effective regulations

a. Development/application of improved tools for field research

This research addresses important weaknesses in drinking water epidemiology studies

through the development and application of better approaches for assessing exposure and health

effects. Methodologic research should be conducted concurrently with the feasibility studies

described below, and the improved methods should be integrated into the design of full scale

studies as they become available. 

HE.D.1 - Improving estimates of residential DBP exposures in epidemiology studies

This includes research described in the Exposure section that has a direct application to

epidemiology studies. Projects EX.D.14 through 16 are particularly relevant to

epidemiology research and also provide information that can be used in assessing risks.

Priority: Variable (see Exposure section)

HE.D.2 - Improving measures of biologic effect: Field evaluation of biomarkers

Field evaluation of morphological, biochemical, and/or molecular alterations that may

result from exposure to DBPs. An initial focus on possible biochemical indicators of male

reproductive toxicity is supported by recent progress in this area in the laboratory. The

development of biomarkers for cancer may provide some important insights into

mechanisms of action. However, the priority of this line of research for supporting

epidemiology studies will depend upon the priority given to new full-scale epidemiology
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studies in the future. [See project EX.D. 15 in the Exposure section on biomarkers of

DBP exposure]

Priority: High

HE.D.3 - Improving methods for managing health and exposure data This ongoing

project is evaluating the use of a geographic information system (GIS) and water quality

modeling in a study of the potential impacts of chlorination and chloramination on

reproductive health of populations in Colorado. GIS, which is a data management and

visualization tool that has been developed for use in other contexts, is assisting in study

design, sample selection, and analysis of data. If effective, this approach could be applied

in future full-scale studies. 

Priority: High

b. Feasibility/full scale studies 

Plans for future epidemiologic research will be influenced by current assessments of

existing data (see Assessment section below), the outcome of epidemiology studies now

underway, and ongoing efforts to improve epidemiologic methods. The availability of suitable

health and exposure data, as well as the amount of resources available, will be key determinants in

the number, types and locations of studies that will be conducted. Some elements of study design

may be similar for both cancer and reproductive outcomes, such as identifying areas with water

quality parameters of interest (e.g., pH, bromide concentration).

Cancer epidemiology studies in communities served by water treated with disinfectants

other than chlorine or chloramine will not be possible due to the unavailability of adequate

historical exposure data. Assessments of potential cancer risks associated with exposure to the

by-products of alternative disinfectants will therefore need to rely upon data from toxicity studies

of individual DBPs and mixtures of DBPs (see toxicology section below). Epidemiology studies

of adverse reproductive outcomes for the various treatment options may be possible since these

studies are not constrained by the need for such long-term exposure data.
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The general goal of the feasibility studies is to demonstrate that an acceptable

epidemiologic test of the possible association between DBP exposures and cancer or noncancer

risk can be conducted. More specifically, the studies must provide reasonable assurances that: 1)

the subjects' exposures to DBPs can be accurately assessed at least over the latent or critical

period of the development of the adverse effects of concern; 2) study sites exhibit water quality

parameters (e.g., bromide levels, pH) and treatment processes of greatest interest; 3) the study

population exhibits enough variation in DBP exposure to allow a dose-response function to be

established; 4) suitable measures or markers of exposure and effect will be used; 5) the test for

DBP effect will not be unduly confounded by factors such as differences in demographic

characteristics, unmeasured exposure to environmental contaminants other than DBPs, and

residential mobility; and 6) the study will have sufficient statistical power across a reasonable

range of sample sizes and odds ratios.

HE.D.4 - Feasibility studies: Cancer To be conducted in communities served by

chlorinated and chloraminated water supplies, with a focus on cancer of the bladder,

colon, rectum, and other possible cancer sites. Reassessment of the existing cancer

epidemiology data (see Assessment Section below) is an essential prerequisite to

determining whether new studies should be carried out.

Priority: High

HE.D.5 - Feasibility studies: Reproductive effects To be conducted in communities

served by chlorinated, chloraminated, and possibly ozonated water supplies. Studies may

focus on at least one of the following endpoints: human fertility and fecundity (male and

female), growth retardation, and common malformations. The few available DBP

reproductive epidemiology studies have been reviewed in several expert workshops

convened by EPA (described above). The research recommendations that have been

developed from these workshops should be considered in the conduct of future feasibility

studies. 

Priority: High
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HE.D.6 - Full scale studies: Cancer and reproductive effects Dependent upon the

findings of Projects 4 and 5 above. May include new studies and/or collaboration with

planned, recently completed or ongoing case-control studies. 

Priority: Dependent upon outcome of feasibility studies. (If feasible, high)

1.2 What is the toxicity of the highest priority chemical contaminants

 and mixtures of DBPs?

State of the Science

The toxicologic literature on individual DBPs has grown considerably over the last 20

years, particularly for the by-products of chlorination. Basic toxicologic information is available

on many of the THMs, HAAs, aldehydes, and miscellaneous organic and inorganic contaminants

found in treated drinking water. A number of these by-products have been shown to cause

cancer, reproductive effects, and various target organ toxicities in experimental animals, though

most commonly at exposure levels that are from one to several orders of magnitude higher than

the ambient concentrations to which people are exposed.

The DBPs that have been studied experimentally represent only a fraction of the byproducts that may be present in treated drinking water. Consequently, there are many

uncertainties in assessing risks based on such limited data. While the ambient concentrations

(typically in the Fg/L range) of many of the known DBPs are likely to be greater than the levels of

most of the other by-products in the complex mixture, there may be poorly characterized or as yet

unidentified by-products that are of concern from a health perspective. For example, the highly

mutagenic by-product MX and related halogenated hydroxyfuranones may be of public health

importance even though they are present in relatively low concentrations in treated drinking

water. The toxicity of many of the brominated, mixed bromochloro, and inorganic by-products

has been inadequately studied. This includes DBPs such as the brominated THMs and MXrelated compounds (formed with chlorination and chloramination), bromate and the brominated

acids (from ozonation and chlorination), cyanogen chloride (from chloramination), and chlorate

(from chlorine dioxide). In addition, nearly all of the available toxicologic data on DBPs pertain
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to individual compounds. There is little information on the toxicity of complex mixtures of DBPs,

or on the toxicologic interactions that may occur between the individual DBPs in a mixture.

Perhaps the most critical underlying issue for toxicologic research on DBPs is the need to

better understand the predictive relationship between toxicologic endpoints and human disease

(i.e., animal-to-human extrapolation). The metabolism of DBPs, and the mechanisms by which

they cause their effects in animals, directly influence the shape of the dose-response curve at low

doses; this has important implications for estimating the risks posed by DBPs to humans.

Whereas the epidemiology data suggest possible associations between DBPs and bladder

or colo-rectal cancer, the experimental carcinogenicity data indicate that the liver and kidney are

the most common target organs for the THMs and HAAs. The main exceptions are the rare

intestinal tumors in animals exposed to bromodichloromethane and bromoform (which

corresponds to the epidemiology data), and tumors of the thyroid and peritoneal mesothelioma in

bromate-treated animals. The mutagenicity of DBPs varies within and between classes, with the

brominated by-products generally more mutagenic than those that are chlorinated. Basic cancer

dose-response information is inadequate for a number of potentially important by-products,

including chlorate, cyanogen chloride, MX, and several of the brominated acetic acids. In

addition, more detailed biologic information is needed to further characterize the carcinogenicity

of dichloroacetic acid, bromodichloromethane, and bromate, which appear to be the most

important by-products from a risk perspective based on a consideration of their estimated cancer

potencies and ambient exposure levels.

Several DBPs have been shown to cause reproductive and developmental toxicity in

laboratory animals, although an examination of the existing data base suggests that the studies

have not been performed in a completely systematic manner. In general, more data are available

on the effects of DBPs on the development of the embryo and fetus than on other parts of the

reproductive process. Recent data from relatively low dose studies of the brominated acids

suggest the need for more detailed investigations of some of these by-products. Screening-level 

data are needed for a number of halomethanes, haloacids, halonitriles, ketones and inorganics
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(particularly bromate). 

The neurotoxicity and immunotoxicity of DBPs in general have not been well

characterized. There are few indications in the literature that these endpoints should be of

concern at ambient exposure levels. Nevertheless, a limited screening effort to evaluate selected

DBPs for these endpoints in a systematic manner is needed to ensure that this assessment is

correct. Preliminary results from studies in rats have shown that relatively low doses of

dichloroacetic acid (similar to the lowest doses at which other noncancer effects have been

observed experimentally) can cause reversible neurotoxicity after exposure periods of three

months. These findings suggest that additional research to characterize the potential

neurotoxicity of dichloroacetic acid and related haloacids is warranted. 

A number of studies have been conducted to address questions concerning the toxicity of

"real world" mixtures of DBPs. These studies, which used either concentrates of drinking water

or humic acid preparations treated with various disinfectants, were largely negative or

inconclusive, and had a number of technical limitations. In addition, a few studies have evaluated

mixtures of drinking water contaminants such as pesticides and other organics, but research on

defined mixtures of DBPs is lacking. Little is known about the possible toxicologic interactions

of individual DBPs in a mixture, i.e., whether their toxicity is additive, as is the current default

assumption, or if their toxicity is either more or less than additive. To address the many issues

relating to toxicology, sample preparation, chemical analysis and assessment, an integrated, crossdisciplinary research effort is necessary.

With respect to the disinfectants themselves, the toxicologic data base on chlorine,

chloramine, and chlorine dioxide is considered variable, although there is generally little health

concern over exposure to the levels of disinfectant residuals commonly found in finished drinking

water. Additional data are needed, however, to better characterize the potential immunotoxicity

of these disinfectants.

EPA is currently conducting hazard identification and dose-response research on a number
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of DBPs across a variety of toxic endpoints. Chronic cancer bioassays have recently been

completed or are near completion for di- and trichloroacetic acid, bromodichloromethane, chloral

hydrate, and bromate. The current focus of mechanistic and pharmacokinetic studies is on

dichloroacetic acid, bromodichloromethane, and Bromate. Research is being conducted at EPA

on the male reproductive toxicity and the embryotoxicity of selected HAAs and THMs. EPA is

also evaluating the neurotoxicity of dichloroacetic acid. These by-products were selected for

more detailed studies because they appear to be of greatest concern from a risk perspective.

The following listing of research activities outside of EPA is incomplete, but is

nevertheless intended to provide some useful information on other important ongoing research. 

In collaboration with EPA, the National Toxicology Program (NTP) has a screening program to

evaluate the reproductive, developmental, and immunotoxic effects of selected DBPs. The NTP

also plans to conduct mechanistic research using short-term models (e.g., transgenic animals) to

evaluate selected DBPs, and will initiate chronic bioassays on several high priority DBPs,

including bromodichloromethane, chlorate, dibromoacetic acid, dibromoacetonitrile and MX. 

Mechanistic research on the carcinogenicity of chloroform is being conducted by the Chemical

Industry Institute of Toxicology. The Chemical Manufacturers Association is conducting a twogeneration rat reproductive study on chlorite. Research in Finland recently completed a study that

demonstrated the carcinogenicity of MX in a chronic cancer bioassay. A cancer bioassay on

dibromochloroacetic acid was recently initiated in Japan.

Research Topics and Priorities

Toxicologic research described in this chapter can be grouped into three distinct

categories: a) hazard identification and dose-response studies to fill data gaps for newly identified

or priority contaminants; b) developing more detailed toxicologic information for the most

important substances, particularly in the areas of pharmacokinetics and mechanism(s) of action to

facilitate extrapolation of data to humans; and c) evaluating the toxicity of simple and complex

mixtures of DBPs. The preferred research approach involves initial screening-level studies of

DBPs to fill data gaps, followed by more detailed research if additional data are needed for

quantitative risk assessment. Toxicology studies of individual DBPs and possibly drinking water
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mixtures will be particularly important for evaluating the relative cancer risks that may be

associated with disinfection strategies other than chlorination and chloramination, since historical

exposures to the by-products of the alternative treatments are too short to evaluate such risks in

epidemiology studies.

The data obtained over the next five years from DBP screening studies and from the more

focused mechanistic studies on selected priority by-products will greatly enhance the assessment

of risks that may be associated with exposure to individual by-products of chlorination and

alternative disinfectants. These studies will also provide insights into the relative risks of different

treatments. It is clear, however, that laboratory studies of DBP mixtures and/or field studies of

human populations represent more relevant approaches for comparing the risks of the various

treatment processes (technical constraints and data limitations notwithstanding). 

a. Hazard identification and dose-response

For many newly identified and some known drinking water contaminants, basic

information is needed to describe their potential toxicity for a variety of endpoints, including

cancer, reproductive and developmental toxicity, and neurotoxicity. An important component of

research to address data gaps, potentially applicable to one or more of the listed toxicity endpoints

and closely aligned with data generation efforts, is the development of structure-activity

relationships (SAR). When sufficient data on related DBPs exist, SAR models can be derived and

used to provide preliminary estimates of toxicity of untested DBPs, prioritize newly identified

chemicals for testing, and in some cases, generate insight into molecular mechanisms of toxicity.

Experimental research to fill data gaps for hazard identification and dose-response

assessment purposes is described below. The cancer dose-response studies and the

reproductive/developmental effects screening studies are high priorities because they will help

identify those DBPs with the highest risk, provide dose-response information that can be used in

conducting better risk assessments, and provide better information to more accurately estimate

costs and benefits of the rules. The neurotoxicity and immunotoxicity studies are medium

priorities because of the lack of published studies demonstrating that these endpoints are of great

concern.
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HE.D.7 - Cancer dose-response studies Two-year exposure studies in laboratory

animals to evaluate the potential carcinogenicity of DBPs, using study designs that will

provide better information for use in Agency risk assessments. Selection of an appropriate

range of doses that will permit an evaluation of the dose-response in the low-dose range

(to the extent possible experimentally) will be a key consideration in the study design. 

These studies also address selected pharmacokinetic and mechanistic questions that will

provide data for use in more biologically based risk assessments (see Projects HE.D.11

and 12). As mentioned above, the NTP is planning to initiate chronic exposure studies on

several high priority DBPs in 1997 and 1998.

Priority: High

HE.D.8 - Reproductive/developmental effects screening studies Evaluation of the

reproductive and developmental toxicity of priority DBPs in standardized screening tests,

and conducting specialized developmental toxicity studies on selected DBPs and

disinfectants (e.g., two-generation studies, research to identify alterations in pregnancy

maintenance and ovarian function). Current priorities in an ongoing EPA/NTP

collaborative screening program include bromate, chlorodibromomethane, bromodichloromethane, bromoacetonitrile, dibromoacetonitrile, and bromochloroacetic acid.

Priority: High

HE.D.9 - Neurotoxicity studies Characterization of the neurotoxicity of priority DBPs,

with an initial focus on dichloroacetic acid and related HAAs. 

Priority: Medium 

HE.D.10 - Immunotoxicity studies Evaluation of the potential immunotoxic effects of

selected high priority DBPs and disinfectants in laboratory animals using a tiered approach

that includes several measurements of immune function. This research will be conducted

in a coordinated effort with NTP.

Priority: Medium 

b. Pharmacokinetics and mechanisms of action
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Research on pharmacokinetics (i.e., distribution, metabolism and elimination) and

mechanisms of action is necessary to interpret the biological significance of an effect and to

provide a sound scientific basis for assessing risk. By describing metabolism, tissue dosimetry and

tissue response, physiologically based pharmacokinetic (PBPK) models and biologically based

dose-response (BBDR) models permit a more accurate prediction of the shape of the doseresponse curve for humans exposed to a particular contaminant. This research also includes the

development of a structure/ activity framework for assessing the toxicity and mechanisms of

action of related DBPs, and provides insights on the development of biomarkers of effect and

exposure. Due to the resource demands and longer time frame for this type of research, only the

highest priority individual DBPs and classes of DBPs are selected for study. As mentioned above,

dichloroacetic acid, bromodichloromethane, and bromate are considered to be three of the most

important DBPs for which this type of detailed information is desirable with respect to cancer. 

Current data suggest that more detailed studies of the reproductive and developmental toxicity of

certain THMs and HAAs are warranted. These projects are considered to be high priority

because they address major uncertainties in the risk assessment process, and focus on the toxic

endpoints of greatest concern. This research is also responsive to the research requirements of

the 1996 SDWA Amendments, which direct the Agency to conduct research to improve the

biological basis for drinking water risk assessments.

HE.D.11 - Pharmacokinetic and mechanistic research to improve cancer risk

assessment for priority DBPs This includes research in two interrelated areas: 1) Studies

to evaluate the pharmacokinetics and toxicity of selected DBPs to obtain better estimates

of metabolism and relevant target tissue dosimetry; 2) Mechanistic studies to evaluate the

physiological, biochemical and molecular changes that accompany the carcinogenic

response. These efforts will provide data to support more biologically based risk

assessments for a small number of the highest priority DBPs, and will in some cases lead

to the development and subsequent validation of physiologically based pharmacokinetic

(PBPK) models and/or biologically based dose-response (BBDR) models. 

Pharmacokinetic and toxicity research at EPA is currently focused on selected THMs and

HAAs, with a primary emphasis on the development and validation of PBPK model for

bromodichloromethane. Mechanistic research is currently being conducted on
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dichloroacetic acid and bromate. These by-products were selected for study because the

results of screening studies, combined with estimates of exposure, indicated that they

could be of greatest importance from a risk assessment perspective. This research is

linked with the dose-response studies described in HE.D.7.

Priority: High 

HE.D.12 - Pharmacokinetic and mechanistic research to improve assessments of

reproductive toxicity and developmental effects for priority DBPs Research to

further characterize the potential reproductive and developmental toxicity of priority

DBPs. Ongoing research is focused on the THMs and HAAs, using a variety of in vitro

and in vivo techniques. Contaminants are selected for these more detailed investigations

on the basis of results of earlier screening-level studies described in HE.D.8.

Priority: High

c. DBP mixtures

As an integral part of a multi-disciplinary effort on drinking water mixtures, toxicology

research can provide the data needed to characterize the relative toxicity of complex mixture

preparations and to evaluate the interactions between key components of the mixture. Important

issues in complex mixtures research include the need to determine the appropriate study design

and to overcome technical problems relating to sample preparation and chemical analysis. The

first two mixtures projects described below represent a phased approach in which a feasibility

study is conducted before attempting full-scale studies to evaluate the relative toxicity of complex

mixture drinking water samples. The feasibility study, as well as the mutagenicity screening study,

are considered high priority because they address a potentially high-risk, high-uncertainty issue,

and they could lead to further research that will provide information on the relative risks of

different disinfected waters. The DBP interactions study can provide useful insights into the

assumptions currently used in assessing risks for mixtures. It is ranked medium because it is a

less-direct approach to assessing the relative risks of complex drinking water samples.

HE.D.13 - Mixtures feasibility study Assessment of the feasibility of studying drinking

water mixtures, and development of a research strategy. This involves the use of
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workshop(s), special consultations and pilot studies, and must be linked to similar

feasibility assessments in related areas (e.g., exposure/chemistry).

Priority: High 

HE.D.14 - Toxicologic evaluation of drinking water mixtures Toxicologic testing and

development of new methods as needed to evaluate the relative toxicity of drinking water

samples that vary by disinfection technique and selected water quality parameters. This

also includes research to identify the individual components or classes of DBPs that

contribute most to the overall toxicity of the mixture.

Priority: Depends upon outcome of Project 13 (High if feasible)

HE.D.15 - Mutagenicity screening studies of drinking water mixtures Use of in vitro

assays to evaluate the relative mutagenicity of complex mixtures of DBPs in concentrated

extracts of drinking water treated with different disinfectants. (ongoing)

Priority: High

HE.D.16 - Studies of DBP interactions Research to evaluate DBP interactions in welldefined mixtures, with an initial focus on the major classes of DBPs (e.g., THMs and

HAAs). This is linked to mixtures assessment activities in Section D, Risk Assessment,

below.

Priority: Medium 

C. EXPOSURE RESEARCH

Approximately 100 different DBPs have been identified in treated drinking water. For

a relatively small number of DBPs, perhaps 10-15, occurrence data are reasonably well established

in terms of concentration ranges typical of source waters and some treatment processes. Major

gaps still exist in our knowledge about what DBPs are formed from different treatment processes,

particularly processes that use alternate disinfectants, such as ozone. Research in this area is

hampered by lack of analytical methods. Uncertainties also exist regarding actual exposures to
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DBPs.

1. What methods are adequate for the analysis of DBPs?

State of the Science

Analytical methods for specific DBPs are either research methods, often the methods used

in the discovery process, or practical methods required for regulatory compliance monitoring or

large-scale exposure surveys. Research methods are usually unacceptable for regulatory use or

even large-scale exposure surveys because they are usually too poorly tested and documented,

relatively complex and costly, and often infested with unexpected problems. Regulatory methods

are desired that are simple, relatively cheap, free of problems, accurate, precise, multi-laboratory

tested, and have method detection limits (MDLs) no greater than 20% of the proposed MCL. 

The requirement of an MDL no greater than 20% of the MCL is highly desirable because this

level is sufficient to ensure that normal measurement variability does not produce an out-ofcompliance measurement when the utility is in compliance.

Very good practical methods of analysis are available for a few of the DBPs, e.g.,

chloroform, bromodichloromethane, chlorodibromomethane, and bromoform (the

trihalomethanes, THMs). These successful practical methods rely on the use of high resolution

gas chromatography (GC) and GC/mass spectrometry, the development of which had an

enormous impact on our ability to discover, identify, and measure thermally stable, readily

extracted, and reasonably volatile organic compounds in drinking water. Thermally stable

volatile compounds are capable of passing into the gas phase without chemical decomposition or

other chemical changes. 

Methods for other byproducts are useable, but further improvement is highly desirable. 

For example, the analytical methods currently used for the haloacetic acids, which are currently

proposed for regulation, are not simple. These methods require a very skilled laboratory

technician and are relatively costly compared to the methods used for the THMs.
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A major and very significant analytical limitation exists for the measurement of polar,

water soluble (difficult to extract), and non-volatile organic and inorganic substances in source

and treated drinking water. The lack of even research methods for these type of compounds has

impeded the capability to identify and conduct exposure studies for additional byproducts,

especially those from alternate disinfectants or from combinations of disinfectants. A major need

is the development of new extraction techniques and instrumentation for the identification and

measurement of polar, water soluble, non-volatile substances in drinking water.

From the exposure point of view, another need is for real-time methods to continuously

monitor finished and source water for DBPs and precursors. Real-time monitoring would provide

information on the temporal variations in the concentrations of DBPs which is needed to

determine the true level of exposure by the consumer. As a by-product of this development,

treatment plants could use these technologies to provide on-line, in-the-plant process monitoring

and feedback control of DBP formation by adjusting process parameters as a function of current

conditions. Current AWWARF-sponsored research on real-time monitoring methods addresses

TOX and TOC, but not disinfectant residuals or by-products.

Smaller treatment plants generally need to rely on commercial laboratories for the analysis

of DBPs due to the relatively expensive equipment requiring highly trained personnel (e.g., high

resolution GC/MS). Development of alternative simpler “kit-like” methods for specific DBPs

would be less expensive, easier to use and may provide better consistency and quality control in

reporting.

Research Topics and Priorities

a. Additional methods or method improvements needed to implement the Stage 1 DBP rule

The improvement of the methods for bromate and haloacetic acids are considered high

priority because they would help in the implementation of the Stage 1 DBP rule. In addition, the

potential health risks posed by these chemicals at potentially low levels requires better analytical

methods to ensure the best possible occurrence data are available when estimating risks. The

evaluation of the TOC method is a high priority because of the importance of TOC in the
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generation of DBPs and the regulatory requirement to measure TOC in the enhanced coagulation

requirements. The development of a more sensitive chlorine dioxide method is a medium priority

because, as discussed in the project description, the need for a more sensitive method is dependent

on the outcome of the CMA two-generation rat study (described in the Health Effects section,

above). The real-time monitoring for disinfectant residuals is a low priority because compliance

with the proposed criteria (MCLs for TTHMs and HAAs) is based on an annual average of

concentrations measured in the distribution system. However, if reproductive/developmental

effects are of a concern, then standards may be established to prevent the threshold level from

occurring anywhere in the distribution system. In this case, real-time monitoring may become

more important. The performance evaluation (PE) studies for DBPs are a high priority because it

is critical that there are sufficient and qualified laboratories for performing analytical work

required by the ICR and Stage 1 DBP rule.

EX.D.1 - Low level bromate (BrO ) measurement The need for a practical analytical 3

- 

method for bromate has been established by the current proposal to set an MCL of 0.01

mg/L. The current standard analytical method for bromate has a serious interference from

chloride at this concentration and the method is not sufficiently sensitive to measure

bromate reliably at the proposed MCL. A recently developed ASTM method has the

potential to reduce the method detection limit (MDL) of bromate ion from 0.02 mg/L to at

least 0.002 mg/L which is 20% of the proposed maximum contaminant level (MCL) of

0.01 mg/L. To be practical, this new method must be validated by multi-laboratory

testing. Lower detection limits are desired for possible use in the stage 2 DBP rule.

Priority: High

EX.D.2 - Improved method for haloacetic acids A recently developed method for the

determination of haloacetic acids reduces some of the concerns about method deficiencies

in extraction, derivatization, and lab safety and it expands the method to include all nine

possible bromo-, chloro-, and mixed bromochloroacetic acids. This new method must be

validated by multi-laboratory testing. The long-term need is to develop a simpler method

that has increased sensitivity. Even more capabilities may be needed for the stage 2 rule.

Priority: High
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EX.D.3 - Expand quality control for TOC, evaluate new TOC methods

The currently proposed DBP rule specifies total organic carbon (TOC) as a required test

method. Several different technical approaches are available and the only documented

method has quality control deficiencies. This project is needed to evaluate the published

methods and instrumentation for TOC to determine whether they can achieve the required

MDLs and precision. A documented method with full analytical quality control directions

will be produced. To be practical, this new method must be validated by multi-laboratory

testing.

Priority: High

 

EX.D.4 - Low-level ClO measurement A more sensitive laboratory method for 2 

chlorine dioxide will be needed if an ongoing CMA study on the reproductive effects of

chlorite shows risk below 0.8 mg/L. The existing method has a detection limit deficiency.

Priority: Medium (until risk is clear; could be elevated to high priority)

EX.D.5 - Real-time monitoring for disinfectant residuals Develop performance

criteria for real-time, on-line, in-the-plant continuous monitoring technologies for

disinfectant residuals to provide in-plant feedback control of their concentrations. This is

needed for the proposed disinfection rule.

Priority: Low (except if developmental or reproductive risks become evident, could be

elevated to high priority) 

EX.D.6 - PE studies for DBPs and disinfectants A requirement of the proposed rules is

that laboratories participate in performance evaluation studies to meet the laboratory

certification requirements of the rules. Some additional research will be required to

develop procedures for preparing, stabilizing, and distributing DBP PE samples and

statistically analyzing the results of the PE studies. Conduct performance evaluation

studies of methods for disinfectants and DBPs.

Priority: High 

b. Methods needed for Stage 2 DBP rule and the longer-term
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The method for peroxides is a medium priority because peroxides are relatively unstable

and decompose to form other substances. In addition, peroxides will be addressed in the Stage 2

DBP rule and therefore there is not an immediate need to develop improved methods. The realtime, in-plant monitoring of DBPs is a medium priority for the same reasons discussed above for

monitoring of residuals. The improved method for aldehydes is a medium priority because of the

uncertainties with the results of the ICR and because this information is not needed for the Stage

1 DBP rule. The priorities of the projects below may change, or additional projects may be

required, depending on the ICR data, project findings under the exposure research described in

the next section, health effects, and risk assessment information. 

EX.D.7 - Methods for peroxides Peroxides are believed to be formed in water treated

with ozone. Exposure issues are uncertain and cannot be answered until research

indicates whether these substances are produced in quantities that would be a concern. 

Develop research methods for the determination of peroxides that may form in water

treated with ozone.

Priority: Medium (5 yrs, $100K for multi-laboratory validation)

EX.D.8 - Real-time, in-plant monitoring of DBPs Develop real-time, on-line, in-theplant or field continuous monitoring technologies for disinfection by-products to provide

data on temporal variations in the concentrations of DBPs for exposure studies and inplant feedback control of their formation. 

Priority: Medium

EX.D.9 - Improved method for aldehydes Aldehydes are formed in water treated with

ozone. A major issue is the reaction of formaldehyde with chloramine (added to provide a

disinfectant residual) to form cyanogen chloride. The method for aldehydes being

proposed for the Information Collection Rule (ICR) is a research method which may not

be a practical method for regulatory compliance monitoring. Develop an improved method

for aldehydes that form in water treated with ozone.

Priority: Medium 
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2. What levels of DBPs are people exposed to via their drinking water supplies, and what is

the population distribution of exposures?

State of the Science

The types and concentrations of by-products that are formed by different disinfectants are

not fully known. A number of factors other than the disinfectant itself are known to influence the

formation and type of DBPs, for example, variation in the amount of organic material in the

source water, pH and water temperature (see Risk Management section of this chapter). Because

the data base is incomplete, not all disinfection scenarios have been thoroughly studied, and there

are few analytical methods for polar, water soluble and non-volatile DBPs, this major question

cannot be answered at this time. 

The complexity of the exposure question is illustrated by a number of additional questions. 

When tap water is used to dilute frozen juices, make ice cubes, take showers, take baths, or make

coffee, are consumers exposed to the same DBPs that are found at the treatment plant or to

different substances? Since 40%-60% of the drinking water ingested by humans is associated

with dietary intake, what effect does food processing and preparation have on DBPs? What

happens to the DBPs found at the treatment plant when the water is stored for long periods in

reservoirs or tanks? What happens to these substances when the water is piped long distances,

trapped for long times in dead-end pipes, or blended with water from different sources that has

been treated differently? Presently we cannot fully answer any of these questions. 

Although the drinking water regulations were intended to protect the consumer, except

for THMs, very little is known about changes in DBPs and other substances that occur in the

distribution system and the actual exposure by people to DBPs. The ICR will provide extensive

DBP occurrence data within treatment plants and distribution systems, but mainly for chlorinated

DBPs. This data will be used for developing and testing models for predicting DBP occurrence at

consumer taps. In addition, several long-term research projects are needed to address these

questions.
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Research Topics and Priorities

a. Characterize types and concentrations of DBPs formed from different disinfectants and

combinations 

Research is needed to better characterize the types and concentrations of DBPs that are

formed with chlorine as a function of water quality and disinfectant conditions. Similarly,

research must address the types and concentrations of DBPs formed with ozone plus chlorine and

chloramines as residual disinfectants, with chloramine alone, and chlorine dioxide alone, as a

function of water quality and disinfectant conditions. The identification of new DBPs from

alternate disinfectants is a high priority because the information from this project in conjunction

with toxicity data can provide estimates of the risks from alternate disinfectants and thus help

answer questions relating to the magnitude of the risks from alternative disinfectants. The

methods for non-volatile DBPs are a high priority because without these methods it will be

impossible to accurately determine the occurrence of non-volatile DBPs and thus estimate the risk

from these chemicals.

EX.D.10 - Identify new disinfection by-products from alternate disinfectants

Identify previously unidentified organic DBPs in drinking water treated with alternative

(non-traditional) disinfectants and determine the effects of operating conditions on DBP

formation. This knowledge will allow more complete exposure assessments and risk

assessments and will not be limited to the examination of XAD resin extracts, but will 

explore alternative extraction schemes.

Priority: High 

EX.D.11 - Methods for non-volatile DBPs Develop extraction methods and advanced

instrumentation to characterize the non-volatile and difficult to extract organic and

inorganic DBPs. This knowledge will allow the development of more practical analytical

methods for both the regulatory program and permit more complete exposure assessments
4-27

and risk assessments.

Priority: High

b. Evaluate factors that affect exposure levels, and assess human exposures to DBPs

All the projects, except the modeling of DBP exposure, are a medium priority because the data

generated from these projects, while important, are not absolutely needed for completing the

Stage 1 or 2 DBP rule (the majority of information on exposure will come from the ICR). The

modeling of DBP exposure is a high priority because this information can be used in reducing the

uncertainty in risk assessments and in providing more accurate estimates of the costs and benefits

of the various rules.

EX.D.12 - DBP changes in distribution systems Characterize the changes that occur in

the distribution system including reservoirs, tanks, dead-end pipes, or in water blended

with product from different sources that has been treated differently. Include the

characterization of DBPs in all exposure field studies that collect drinking water samples. 

This work should be coordinated with distribution system studies in the Risk Management

section. The results will allow more complete exposure assessments and risk assessments.

Priority: Medium

EX.D.13 - DBP interactions with foods and associations with dietary intake

Determine what effects disinfectants and DBPs have when they interact with other foods,

e.g., frozen juices, coffee, etc. Determine what other substances are formed that impact

human exposure and contribute to the risk assessment. Determine the influence of food

preparation factors such as temperature and storage on the degradation of DBPs.

Priority: Medium

EX.D.14 - Exposure to DBPs through showering and other household tapwater uses

Determine human exposure to volatile DBPs through inhalation and dermal exposure

during hot showers and hot tub baths. Expand limited existing data on trihalomethanes to

the potentially more significant haloacetic acids, haloacetonitriles, haloketones, aldehydes,
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etc. Existing data on human activity patterns and existing household exposure models

should be used. These exposure data are needed to complete the risk assessment.

Priority: Medium

EX.D.15 - Markers of DBP exposure Discover the underlying biochemical reactions

related to exposure by people to DBPs and use these as biochemical markers of human

exposure. Do DBPs react with DNA or proteins and can markers of this exposure be

found? This information could be critical to long-term risk assessment.

Priority: Medium 

EX.D.16 - Models of DBP exposure Develop models of human exposure to disinfectants

and DBPs and validate these models with actual exposure data. The goal of this model

development is to allow the calculation of actual human exposure to a variety of DBPs

given knowledge of precursors in the source water, the treatment technology,

consumption patterns, and the model being developed for the decay of disinfection

residuals in the distribution system (see Risk Management section, project 3). Various

models will be developed using surveys and ICR data.

Priority: High

EX.D.17 - Exposure as a function of population distribution Conduct a series of

studies to identify exposure as a function of age, behavioral patterns and environmental

factors that affect water consumption. These studies should be done in conjunction with 

project EX.M.22.

Priority: Medium 

EX.D.18 - Tap water consumption and chemical contaminants The results will

consist of two sets of tables. One set of tables will provide tap water intake in terms of

milliliters/person/day and the other will be in terms of milliliters/kilogram bw/day. The

tables will provide estimates of the mean with intervals, as well as estimates of the median

with 90 , 95 and 99 percentiles. In addition, the tables will provide the sample size and th th th
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estimated population for each distribution. Graphics for selected distributions will also be

included. Further, tap water intake will be analyzed based on economic status and age;

race and age; residential status and age; and geographic region and age. The four

geographic regions include: the Northeast, South, Midwest and West.

Priority: High

D. RISK ASSESSMENT RESEARCH

Critical to establishing a regulatory strategy for drinking water is identifying those

contaminants which pose the greatest risk to human health and consequently, what treatments can

be used to reduce these risks and at what cost. To characterize the magnitude and severity of

adverse health effects associated with exposures to DBPs it is necessary to use the methods and

tools of risk assessment. The central role of the risk assessment is to evaluate the scientific data,

and to provide risk managers with qualitative and quantitative estimates of risks posed by specific

waterborne agents. With this information different risk reduction options can be developed. 

Through the development and application of consistent methods and tools for integrating and

interpreting the scientific data, risk assessment studies can provide the framework for comparing

chemical and microbiological risks. Ideally such comparisons would be made on information

taken from studies involving exposure to mixtures of DBPs and microbes actually present in the

source and drinking water of various treatment and distribution systems. However, this is often

not possible because of the lack of information on these whole mixtures, or alternative approaches

for assessing multiple exposures and effects. 

Congressional interest has recently focused on risk based decision making, with emphasis

on better risk characterizations and on reducing uncertainties in risk assessment. The risk

characterization should incorporate more realistic exposure scenarios, identify populations at high

risk especially children, provide where feasible quantitative analyses of uncertainty and sensitivity

analyses, and include estimates of risks from exposures to chemical mixtures. Risk

characterization and comparison of DBPs and microbes, the final product of the risk assessment,

will also provide perspective on assumptions and areas of uncertainty in the risk and exposure
4-30

assessments.

1. How can we characterize the risk posed by exposure to specific and multiple or complex

mixtures of DBPs in drinking water?

State of the Science

Current approaches for characterizing the risks associated with exposures to D/DBPS in

drinking water contain many assumptions and uncertainties. Many of these problems relate to

deficiencies in the underlying scientific data bases for individual contaminants and mixtures and

the methods and models used in risk assessment. As mentioned before, much of the uncertainty in

conducting risk assessments arises from not knowing what DBPs are formed and from a lack of

toxicity data including inadequate human data, insufficient understanding of the mechanisms of

toxicity, extrapolation of animal data to human and lack of interactions data for mixtures. 

Because of this lack of information, risk estimates for DBPs are only possible for a limited number

of individual contaminants, and only qualitatively for disinfected waters from epidemiology

studies. Consequently, EPA has developed a phased approach for characterizing the risks posed

by exposure to DBPs. First, single chemical assessments will be conducted using improved

methods for both qualitative and quantitative assessments of human risks associated with

exposures to drinking water. Particular emphasis will be given to addressing risks to children,

pregnant women and elderly. In addition, EPA will evaluate previously conducted epidemiology

studies to provide better estimates of actual risks based on existing information, and to assist in

designing future epidemiology studies, if warranted. In the second phase, assessment efforts will

use the information on dose and toxicity for single chemicals to predict risk associated with

definable mixtures of agents, and to develop methods to assess risk based on generalizations

across classes of DBPs.

Much scientific progress has been made in the development of alternate models for

estimating noncancer risks levels for single chemicals. Traditionally, EPA risk assessments have

been based on the most sensitive endpoint and data set unless it could be demonstrated that this

endpoint was not relevant to human toxicity. Alternate approaches to analyzing data are being
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investigated to calculate risk estimates that use more of the available data and result in a risk

assessment in which there is greater confidence both statistically and biologically. Because these

approaches use more of the available data, they provide risk estimates that are closer to the actual

risk. Because the methods incorporate varying endpoints and severity, some expression of the

risk of adverse health effects from chemical exposures in excess of the MCLG can be developed. 

Depending on the nature of the data available, estimates using these models can provide incidence

rates for any of the effects occurring in an exposed population. However, these models have been

developed and tested using empirical data sets only and applied to a few well-studied pesticides. 

The application of these models for developing drinking water standards has not been tested nor

compared with estimates developed using current approaches. 

Additionally, EPA is revising the cancer risk assessment guidelines to place greater

emphasis on route of exposure and mode of action when assessing the carcinogenicity of

chemicals. The revisions will also recommend chemical-specific determinations of whether the

dose response is linear or nonlinear, thus providing for a different quantitative approach than the

no-threshold linearized multistage model.

As mentioned in the health effects research, EPA conducted a workshop on scientific

considerations for conducting epidemiologic studies for cancer and exposure to chemical by

products of drinking water disinfectants. The participants concluded that current studies are

insufficient to conclude that the reported associations are causal or provide an accurate estimate

of the magnitude of human risk. In addition to the recommendations discussed previously, the

workshop participants suggested reanalysis of previously conducted interview-based case control

studies using improved exposure estimates and analytical methods to determine the validity of

these risks and to address confounding factors and bias not adequately excluded in previous

reports such as Morris, et al. Reassessment of existing data will also assist in the design of

feasibility studies for cancer and reproductive/developmental effects and determination if full-scale

studies are warranted by addressing systematic errors and biases of previous studies.

In addition to applying improving risk assessment methods for individual DBPs,

advancements are being made in risk assessment methods for mixtures. Typical human exposures
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to DBPs are from low doses of multiple chemicals from multiple routes and can be either

continuous, episodic, chronic, subchronic or acute exposures. However, most of the available

laboratory toxicity data provide information on single chemicals or binary pairs rather than on the

mixture as a whole. Additionally, animal laboratory studies on whole mixtures have been

hampered by the difficulty of developing representative concentrates of DBP mixtures. 

Therefore, established drinking water standards are based on risk assessments for individual

chemicals and epidemiologic data. The Agency has not yet characterized risks from interactions

among pollutants and their consequent effects on human health. The movement toward complete

risk characterizations incorporates a need to realistically describe exposure scenarios at various

drinking water facilities and thus to include the risks from exposures to chemical mixtures.

However, for any mixture of concern, data are generally insufficient to characterize the

risks: not all components of the mixture will be known, the proportions of the known components

will be uncertain, interaction effects data on combinations of the components will be sparse, and

epidemiologic data on human health effects will be rare. Currently, EPA is developing drinking

water feasibility studies that will provide better methods for identifying and quantifying mixtures

components, improve sample preparation and study design for animal testing, and improve the

analytical tools needed to use human data.

Despite these limitations, significant advances have been made in theoretical development

and application of risk assessment methods for characterizing the risks from complex mixtures. 

These methods use data from single chemical components or similar mixtures to generalize across

classes of chemicals or mixtures. If studies cannot be designed to adequately address the issues

described above, then the application of these methods along with improved exposure data and

health information on simple mixtures can be used as alternative methods for estimating risks from

more complex mixtures.

In addition to specific drinking water projects, EPA is conducting research in other

problem areas to develop scientifically valid approaches for implementing PBPK models and

sensitivity analysis in mixtures risk assessments. This research is aimed at identifying those

parameters which most influence the dose response for a chemical or mixture. Research is also
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being conducted that will test approaches for assessing risks for complex mixtures using both

observational data on the mixture itself from existing human studies and data on individual

components of the mixture. These methods may have application to drinking water mixtures once

validated.

The Agency has recently released a risk characterization policy that addresses the need for

more informative and consistent approaches for communication of Agency risk assessments to

decisions makers and the public. The risk characterization provides an evaluation of the

assumptions, uncertainties, and selection of studies and models used in the risk assessment. 

Development of a risk characterization will be required for every Agency risk assessment.

Research Topics and Priorities

a. Characterizing risks of individual DBPs

In order to characterize the risks associated with exposure to disinfectants and disinfectant

by-products, quantitative risk assessment models that have been developed for dose-response

modeling need to be applied to both existing human data and animal laboratory data. Estimates

developed by improved methods need to be compared against existing values in order to address

uncertainties and assumptions. These projects are high priority because they will be used to

establish MCLGs, provide information needed for characterization of risks for each chemical, and

provide information for conducting cost and benefit analysis. 

 RA.D.1 - Cancer risk assessments (Ongoing) Reanalyze cancer risk assessments for

D/DBPs including chloroform, bromodichloromethane, dibromochloromethane and

bromoform, di- and trichloroacetic acid, chloral hydrate and bromate using the revised

Agency cancer risk assessment guidelines and improved dose-response modeling where

appropriate. Reassessments of cancer dose-response data and risk characterizations have

been completed for DCA and chloroform applying the new cancer guidelines. A

workshop was conducted by ILSI to discuss these case studies and an independent expert

peer review panel is evaluating case studies.

Priority: High
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RA.D.2 - Cancer combination study for bromates Case study examining the validity of

combining bromate data sets prior to modeling and calculating a pooled slope factor. Also

includes the modification of risk assessment software to support computer program for

use in developing other DBP cancer estimates. Several papers have been published in peer

reviewed journals. In addition this method has been presented in the proposed cancer

guidelines and as such has undergone extensive peer review and public comment as an

alternative statistical approach for assessing dose-response data. Case study for bromate

has been completed and a journal publication is being developed.

Priority: High 

RA.D.3 - Noncancer risk assessments (Ongoing) Prepare full risk assessment for

disinfectants and DBPs, including di- and trichloroacetic acid, bromo and

dibromochloroacetic acid, four THMs, chlorine, chlorine dioxide, chloramine, chlorite and

chloral hydrate. Incorporate benchmark and categorical regression analyses. A

benchmark for TCA has been completed and presented at the Society of Toxicology

meetings in March 1997. A journal article is in preparation. Additional assessments will

be conducted on high priority Stage I and Stage II DBPs as newer data become available. 

In addition preliminary assessments will be conducted on newly identified DBPs to identify

data gaps and research needs.

Priority: High

RA.D.4 - Risk characterization Develop risk characterizations for selected disinfectants

and DBPs which implement the revised Agency policy. Risk assessments for chlorine,

chloramine, chlorine dioxide and chlorite, THMs, HAAs and chloral hydrate, and bromate

have been developed; however, the uncertainties and assumptions associated with those

risk estimates have not been fully characterized. Include the development of a risk

characterization model for estimating variance in uncertainty factors applied to cancer and

noncancer estimates; particular emphasis will be given to identifying and characterizing

risks to children and higher-risk subpopulations. This will be particularly useful in

comparing cancer estimates (i.e. upper-bound vs maximum likelihood estimates). In

preparation for the final promulgation of Stage I DBP Rule a risk characterization is being
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developed for chlorine and chloramine as well as several other DBPs.

Priority: High

b. Characterizing risks from chlorinated waters

Although many of the epidemiologic studies have methodologic problems or systemic biases that

limit the interpretation of results, the application of consistent statistical tools and improved

methods and data on exposure to chlorinated water or DBPs will provide greater understanding

of the reported risks. Reassessment of existing data will address confounding factors identified in

earlier studies and assist in the design of feasibility studies for cancer and

reproductive/developmental effects and determination if full-scale studies are warranted. These

studies are high priorities because they are aimed at reducing uncertainties in cancer and

reproductive assessments and providing more realistic estimate of actual risks as well as a

common methodology for evaluating risks associated with chlorinated water. In addition, where

possible quantitative estimates will be used for comparative risk analyses with risks from

pathogens.

RA.D.5 - Evaluate newer epidemiologic studies (Ongoing) Four new studies

evaluating the possible association between drinking water and adverse health outcomes

have been conducted since the publication of the meta-analysis of chlorinated drinking

water studies. A review of these studies and data using methods/approaches applied to

earlier studies is being conducted to assess their impact on previous findings. The results

of this analysis will be included in the meta-analytical report currently being developed and

included in the peer review workshop. 

Priority: High

RA.D.6 - Assessment of previously conducted studies (Ongoing) The objective of this

effort is to develop and apply consistent statistical tools and improved methods for

analyzing existing epidemiologic studies and data. Primary focus is to address

confounding factors and biases identified in earlier studies and to assist in the design of

future human studies. Reanalysis of a previous meta-analytical report is being conducted

using several different meta-analytical parameters not previously applied. To date,
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previously published epidemiologic studies of total and various site-specific cancers,

including bladder and rectal cancers, have been reviewed and reevaluated as to their

suitability for providing a valid summary estimate of relative risks. A comprehensive reevaluation of the application of meta-analytical techniques to these data has been

completed. A combination peer review/public participation workshop will be conducted

to evaluate the technical merit of this report and implications for future epidemiologic

studies and assessments in this area. The workshop will be conducted in the Fall of FY

97.

Priority: High

RA.D.7 - Identify ongoing cancer studies (Ongoing) Identify cohort studies of dietary

and case control studies of cancer risks recently planned or compiled or being conducted

in areas with water exposures of interest. This information will assist in determining the

need for future studies, targeting geographic areas for future studies and study design. 

Priority: High

c. Methods and models to characterize risks from mixtures

Scientific advances in the development of innovative risk assessment tools in the area of

study design, statistical methodology and computers models have been developed to estimate

health risks from exposures to chemical mixtures. 

For any mixture of concern, it is not possible to test all combinations of the components;

therefore, risk assessors need methods that can be used to generalize risk estimates from the data

that do exist. With this goal in mind, several feasibility studies have been designed to test their

application to drinking water. Included in this research are models that characterize interactions

of chemicals (i.e., synergism, additivity, or antagonism). These studies will provide estimates

based on realistic exposure scenarios i.e., multiple chemicals, multiple routes. Another expected

result from these studies will be the development of experimental design methods for assessing

risks of multiple chemicals; currently, much of this research cannot be conducted using laboratory

studies because of the large number of test animals needed. 
4-37

These methodologies, if successfully developed, would have enormous impact on the

evaluation of risk from exposure to multiple chemicals at drinking water treatment facilities and

for source water quality studies. These studies are high priorities because they can provide better

methods for quantifying the risks from mixtures, reduce the uncertainty in the current risk

estimates for mixtures, and provide a framework for estimating relative risks associated with

drinking water.

RA.D.8 - Characterization of interactions for mixtures of DBPs Develop procedures

and conduct studies to extract, evaluate and summarize interaction data from a number of

studies and combine the results across studies and endpoints to define the type of

interaction i.e., additivity, synergism or antagonism. This research involves the combining

of risk estimates for mixtures of DBPs. It involves both biological and statistical

evaluations of mixture data. Issues include, but are not limited to, similarity of mechanism

of action across DBPs, incorporation of interaction data into risk estimates,

appropriateness of combining data, and the analysis of variability and uncertainty of risk

estimates.

Priority: High

RA.D.9 -Threshold studies for D/DBPs Research is being conducted to build a doseresponse plane using experimental data from a mixture of trichloromethane,

bromodichloromethane, dibromochloromethane and trichloromethane under the

assumption of additivity for the single components. For any given point on this plane, the

threshold for an adverse effect can be estimated for the mixture. Health effects data for

the mixture are being developed by EPA and will be used to determine if the whole

mixture response is greater or less than the additive, and also to test study design. Effort

includes development of computer algorithms, testing of epidemiologic data and the

development of an optimal study design for laboratory studies of mixtures. Goals include

the detection of interaction effects, establishment of thresholds for the mixtures tested,

comparison of chlorination with ozonation DBP mixtures relative toxicity by testing

proportions of THMs reflecting actual treatment formation. Work is being conducted in

two animal system models thereby allowing for the investigation into interspecies scaling
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factors. 

Priority: High

RA.D.10 -Use of QSAR model to estimate risk for single components and classes of

compounds within a mixture Estimate an adverse effect level for DBPs with limited or

no health effects data using QSAR. EPA data on mixtures of DBPs formed following

various treatment trains such as chlorination plus chloramination could be used to estimate

LOAELs or genotoxic potential for single components and whole mixtures. Compare

predicted estimates to measured values to confirm the accuracy and precision of the

model. Primary focus for this effort is to evaluate and apply a system that can be used in

conjunction with other short-term tests for estimating effects and relative risk levels. 

Additionally, efforts are being directed to employing this model in prioritizing and

selecting newly identified DBPs of potential concern. Research is focused mainly on State

II and future DBP assessment efforts. Currently, thirty DBPs are being evaluated.

Priority: High

d. Methods and models to compare risks

Comparative risk assessment is a relatively new initiative in risk assessment that has not

been well defined. The result is a variety of definitions, approaches and applications. For

drinking water, the focus is to develop a comparative risk model to measure and compare the

known and potential health risks that might result from exposure to multiple stressors transmitted

from the same drinking water source. For example, acceptably treated drinking water serves as a

source of chemical (DBPs), biological (microbial), and physical (distribution system

characteristics) stressors. Exposure to these stressors may result in a variety of adverse health

outcomes including acute and chronic gastrointestinal illness, cancer, liver toxicity, and

reproductive and developmental disorders. Despite scientific advances in identifying and

quantifying the risks associated with any individual stressor, an appropriate methodology has not

been developed that would allow us to assess these different risks in a similar way in order that

they can be compared in a meaningful way. In addition, there is a paucity of data on the nature

and magnitude of risk from these stressors. 
4-39

RA.D.11 - Comparative risk analysis Current comparative risks models for drinking

water weigh the outcomes of microbial exposures to that of cancer from selected DBPs. 

Research needs to be conducted on a variety of models and methods that will allow for the

development of a comparative risk assessment model which addresses multiple outcomes

(e.g., cancer, developmental, reproductive, neurotoxic effects), their impacts and costs. 

This research should focus on the risk analysis and risk reduction benefits derived from

minimizing exposures that would result in adverse outcomes other than cancer. Data will

be developed for use in the regulatory modeling effort described in Chapter III. A

comparative risk framework and strategic model has been developed for DBPs and is

currently being validated and reviewed. SAB formal review of this approach is scheduled

for the Spring of FY 98.

Priority: High

E. RISK MANAGEMENT RESEARCH

How effective are various treatment processes in minimizing 

and controlling the formation of DBPs?

State of the Science

Naturally occurring materials, such as humic and fulvic acids and bromide, which are

present in many surface water sources react with chemical disinfectants to produce disinfection

by-products. Factors affecting the formation of disinfection by-products include the nature of the

source water and content of precursor materials, the water temperature and pH, and conditions

under which the disinfectant is used, such as the concentration, contact time, point of addition,

and the residual maintained. Control strategies must consider these factors because they affect

both the formation of specific by-products and other potential risks. For example, raising the

water pH to control lead corrosion may decrease the formation of haloacetic acids, but it

increases trihalomethane formation and results in a species of chlorine that is a less effective
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disinfectant.

Several options are available for the control of disinfection by-products: 1) removal of

precursor material before disinfection, 2) changes in the disinfection process or use of a

disinfectant that will minimize the formation of selected by-products, 3) removal of disinfection

by-products after they are formed. The various treatment technologies are very similar with

regard to their overall effect on disinfection by-product formation. Disinfection by-products tend

to increase in time so that moving the point-of-disinfection to the end of the water treatment

process is an inexpensive modification that can reduce the formation of by-products without

substantially increasing microbial risks, provided an adequate disinfection contact time is

maintained. Appropriate coagulation and clarification can effectively remove precursors, and this

treatment can be adjusted for the enhanced removal of natural organic matter, thereby minimizing

by-product formation potential. 

Numerous studies have been conducted on DBP formation and control. Early bench-scale

studies conducted by EPA, AWWARF and others examined the factors affecting the formation of

trihalomethanes (THMs), the kinetics of the reaction, and means of assessing precursor, i.e., THM

formation potential (THMFP). Numerous field-scale studies were conducted examining

modifications to the practice of chlorination, alternatives to chlorine (chloramine, chlorine dioxide

and ozone), and removal of precursor, principally by granular activated carbon (GAC). More

recent research conducted by AWWARF and EPA has included haloacetic acids (HAAs), total

organic halide (TOX), chloral hydrate (CH), haloacetonitriles (HANs) and other DBPs as targets

for removal. Isotherms and kinetic studies are being conducted to provide inputs to GAC models

and improved GAC models were developed. Numerous pilot- and full-scale GAC studies are

being conducted in the field, including on-site reactivation of spent GAC. Other means of

precursor control are currently being studied, including membranes, enhanced coagulation and,

more recently, biological filtration. The ICR will collect bench- and pilot-scale data characterizing

GAC and membrane performance on high TOC waters throughout the U.S.

Results from the research to date indicate that enhanced softening may be effective in

removing Total Organic Carbon (TOC) which is a measure of the precursor material for
4-41

disinfection by-products. Studies have also shown that biological filtration may be an effective

tool for removing both precursors and protozoa simultaneously. It was also learned that control

of pH in biological and conventional treatment can minimize the formation of the five haloacetic

acids to be regulated. Membranes have shown promise for removing precursors and pathogens

simultaneously and may be especially useful in small-system applications. Although biological

treatment using ozone is effective for removing precursors and controlling protozoans, it has byproducts of its own that must be evaluated.

Critical questions that must be answered are as follows: To what extent can surrogates be

used to indicate effectiveness of treatment, e.g., TOX, TOC; and, what operational concerns

pertain to the different technologies? The projects selected for research in this section are

intended to define the variables that influence the formation of DBPs. These projects also address

concerns of the simultaneous reduction of risks from microbial and chemical contaminants.

Bench- and pilot-plant studies will initially be conducted to assess different technologies

and approaches. This will be followed by field studies (see RM.M.5) to evaluate the more

promising technologies. In general, these field studies will be conducted at sites where these

technologies are being utilized by certain utilities, such that we can conduct parametric

evaluations of the important operating parameters and make comparisons with full-scale

operations.

Research Topics and Priorities

a. Effectiveness of different treatment processes in reducing DBP precursors (as a function

of water quality and system size)

Research is needed on the effects of enhanced coagulation and enhanced softening on the

operation of filtration processes. Recent EPA studies indicated the pH of filter operation was

critical to aluminum solubility and filter run time, and that membrane materials are fouled by

different types of organic substances. For utilities facing control of both precursors and

pesticides, assessment of their control by oxidative and biological processes is needed. The
4-42

causes and prevention of membrane fouling, and the reliability of scaling up from bench-scale

membrane studies need to be evaluated. 

Projects that develop treatment and operational criteria for technologies for DBP

precursor removal and also assess their efficacy to reduce microbial or chemical contaminants

were all considered a high priority. The membrane scale-up and fouling research was assigned a

medium priority because results from a related AWWARF study and data provided by utilities as

the result of their ICR membrane studies may prove adequate.

RM.D.1 - Enhanced softening for precursor and pathogen removal

Assess TOC removal by lime softening. Study filter operations associated with enhanced

softening. Assess filter run time, particulate and pathogen control, and corrosion

implications downstream of enhanced softening.

Priority: High

RM.D.2 - Effects of ozonation and biofiltration for control of precursor, pathogens

and for pesticide removal

a. - Control of precursor, pathogen and pesticide removal Evaluate ozonation and

biofiltration for control of precursors and pathogens. Assess oxidation and

biodegradation of precursor materials. Include control of pesticides by ozonation and

biodegradation. 

Priority: High

b. - Effect of pH on ozonation and enhanced coagulation Evaluate the effect of

pH on ozonation and enhanced coagulation. Recent EPA studies indicated levels near

the proposed Stage 2 MCLs for TTHM and HAAs could be met with these processes. 

It has been found that low pH enhances coagulation and minimizes bromate formation. 

High pH promotes oxidation by hydroxyl radicals. Study variations in pH since pH

affects aluminum solubility and filter run time.

Priority: High
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RM.D.3 - Analyze ICR data from GAC, membrane bench and pilot studies

Analyze data collected from ICR activities involving bench and pilot studies using GAC

and membrane technology. Cost and performance data will be developed from this

project.

Priority: High

RM.D.4 - Removal of DBP precursors by GAC and membranes ICR bench and pilot

studies will provide performance and cost data for different water quality conditions.

a - Evaluation of membrane reliability Evaluate membrane reliability for multiple

contaminant removal using bench and pilot studies. Conduct a pilot study at a fullscale water plant to evaluate nanofiltration.

Priority: Completed

b - Evaluation of GAC Evaluate GAC for multiple contaminant removal at bench

and pilot scale.

Priority: Completed

RM.D.5 - Membrane scale-up and fouling Conduct bench- and pilot-scale membranes

studies in parallel to assess the appropriateness of bench-scale membranes to predict

larger-scale performance. Examine techniques to limit membrane fouling.

Priority: Medium

b. Effectiveness of using different disinfectants in limiting DBP formation

Research is needed on the use of biological treatment for the control of ozone DBPs, and

the control of Assimilable Organic Carbon (AOC) and Biologically Degradable Organic Carbon

(BDOC). AOC and BDOC are measures of microbial nutrients that could promote distribution

system regrowth. Questions to be answered include: to what extent can chlorite/chlorate byproducts of Cl02

 be removed or formation limited; to what extent can bromate formation be

limited while using ozone; and, for which water qualities are combinations of ozone/chloramines

appropriate for primary residual disinfections without increasing bacterial growth? Because
4-44

ozone promotes regrowth of organisms in distribution systems, nutrient control is very important. 

Improving the understanding of how, and the extent to which ozonation by-products and AOC

formation can be controlled is considered a high priority for assessing the risks and the benefits

associated with the use of ozone. 

RM.D.6 - Ozone by-product formation and control

Evaluate technologies for control of AOC and BDOC. Examine factors affecting

formation of ozone DBPs, AOC and BDOC by ozonation and control by biofiltration. 

Assess bromate formation. This project relates to RM.M.14 and RM.M.26.

Priority: High

c. Small systems technologies for precursor and DBP control

Small systems pose a special problem because of the economic limitations on most small

communities. Developing inexpensive, low maintenance technologies to control disinfection byproducts is considered a high priority.

RM.D.7 - Membranes/advanced oxidation & other technology combinations 

Preliminary results indicate that a combination of ultrafiltration membranes with advanced

oxidation processes results in reduction of organics, lower DBP formation, and less

mutagenicity than typical treatment trains with post-chlorination. Conduct additional

investigations of these approaches individually and in combination for oxidation processes

as UV, UV irradiated Ti0 , iodinated resins, hydrogen peroxide, and on-site mixed oxidant 2

generators.

Priority: High
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Table IV-2

Research Priorities for Health Effects for Disinfection By-Products 

Research Topics Proposed Projects Priorities

DBP Epidemiology 

a. Development/application HE.D.1 - Improving estimates of residential DBP *

of improved tools for field exposures in epidemiology studies

research HE.D. 2 - Improving measures of biologic effect: High

b. Feasibility/full scale HE.D.4 - Feasibility studies: Cancer High

studies HE.D.5 - Feasibility studies: Repro effects High

Field evaluation of biomarkers

HE.D.3 - Improving methods for managing health High

and exposure data

HE.D.6 - Full scale studies: Cancer and repro **

DBP Toxicology

a. Hazard identification and HE.D.7 - Cancer dose-response studies High

dose-response HE.D.8 - Repro/developmental effects screening High

b. Pharmacokinetics and HE.D.11 - Pharmacokinetic and mechanistic High

mechanisms of action research -cancer

c. DBP mixtures HE.D.14 - Toxicologic evaluation of mixtures **

studies

HE.D.9 - Neurotoxicity studies Medium

HE.D.10 - Immunotoxicity studies Medium

HE.D.12 - Pharmacokinetic and mechanistic High

research - reproductive effects

HE.D.13 - Mixtures feasibility study High

HE.D.15 - Mutagenicity screening studies of High

mixtures

HE.D.16 - DBP interactions Medium

 See projects under part 2.b. of DBP Exposure section. *

 Priority depends upon outcome of feasibility studies. **
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Table IV-3

Research Priorities for Exposure to DBPs

Research Topics Proposed Projects Priorities

DBP Methods

a. Additional methods or method EX.D.1 - Low-level bromate measurement

improvements needed to implement the EX.D.2 - Improve method for haloacetic

Stage 1 DBP rule acids

b. Methods needed for Stage 2 DBP EX.D.7 - Methods for peroxides

rule and the longer-term EX.D.8 - Real-time, in-plant monitoring of

EX.D.3 - Expand quality control for TOC,

evaluate new TOC methods

EX.D.4 - Low-level ClO measurement 2

EX.D.5 - Real-time monitoring for

disinfectant residuals

EX.D.6 - PE studies for DBPs and

disinfectants

DBPs 

EX.D.9 - Improved method for aldehydes

High

High

High

Medium

Low

High

Medium

Medium

Medium

DBP Exposure

a. Characterize types and concen- EX.D.10 - Identify new disinfection by- High

trations of DBPs formed from different products from alternate disinfectants

disinfectants and combinations EX.D.11 - Methods for non-volatile DBPs High

b. Evaluate factors that affect exposure EX.D.12 - DBP changes in distribution Medium

levels, and assess human exposures to systems

DBPs EX.D.13 - DBP interactions with foods Medium

EX.D.14 - Exposure to DBPs through Medium

showering

EX.D.15 - Markers of DBP exposure Medium

EX.D.16 - Models of DBP exposure High

EX.D.17 - Exposure as a function of Medium

population distribution

EX.D.18 - Tap water consumption High
4-47

 Table IV-4

Research Priorities for Risk Assessment for DBPs

Research Topics Proposed Projects Priorities

a. Characterizing risks of RA.D.1- Cancer risk assessments High

individual DBPs RA.D.2- Cancer combination study for bromates High

b. Characterizing risks from RA.D.5- Evaluate newer epidemiologic studies High

chlorinated waters RA.D.6- Assessment of previously conducted High

c. Methods and models to RA.D.8 - Characterization of interactions for High

characterize risks of DBP mixtures of DBPs.

mixtures RA.D.9 -Threshold studies for D/DBPs High

d. Methods and models to RA.D.11 - Comparative risk analysis High

compare risks

RA.D.3- Noncancer risk assessments High

RA.D.4- Risk characterization High 

studies

RA.D.7- Identify ongoing cancer studies High

RA.D.10 -Use of QSAR model to estimate risk for High

single components and classes of compounds

within a mixture
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Table IV-5

Research Priorities for Risk Management of DBPs

Research Topics Proposed Research Priorities

a. Effectiveness of different RM.D.1- Enhanced softening for precursor and High

treatment processes in pathogen removal

reducing DBP precursors (as RM.D.2- Effects of ozonation and biofiltration for

a function of water quality control of precursor, pathogens, and for pesticide

and system size) removal

 a. Control of precursor, pathogen, pesticide removal High

 b. Effect of pH on ozonation and enhanced

coagulation High

RM.D.3- Analyze ICR data from GAC, membrane

bench and pilot studies High

RM.D.4- Removal of DBP precursors by GAC and 

membranes Completed 

RM.D.5 - Membrane scale-up and fouling

Medium

b. Effectiveness of using RM.D.6 - Ozone by-product formation and control High

different disinfectants in

limiting DBP formation

c. Small systems RM.D.7 - Membranes/advanced oxidation & other High 

technologies for precursor technology combinations

and DBP control